Epigenetic modification enhances the cytotoxicity of busulfan and 4-hydroperoxycyclophosphamide in AML cells
Busulfan (Bu) is a bifunctional DNA alkylating agent commonly used in combination with other agents for high-dose pre-transplant conditioning therapy for hematopoietic stem cell transplantation (HSCT) [1]. Its combination with cyclophosphamide (Cy) has been used as an alternative to a Cy-total body irradiation (TBI)-containing myeloablative regimen and found to be effective for acute leukemias [2-7]. The “BuCy2” preparative regimen is more effective than Cy+TBI in patients ≤ 40 years old [6,8]. However, the “BuCy2” regimen is commonly associated with high non-relapse mortality [9]. (Source: ...
Source: Experimental Hematology - August 10, 2018 Category: Hematology Authors: Benigno C. Valdez, Xiaowen Tang, Yang Li, David Murray, Yan Liu, Uday Popat, Richard E. Champlin, Borje S. Andersson Source Type: research

Fluorescent genetic barcoding for cellular multiplex analyses
Hematopoiesis depends on the hierarchical production of mature cells from a pool of self-renewing hematopoietic stem cells (HSC). Due to their high regenerative capacity, great interest focuses on the understanding of HSC biology, which can be best assessed in functional transplantation assays that allow for the read-out of HSC numbers and their potential to produce cells of disparate lineages. To track individual HSC fate decisions, initial transplantation studies employed retroviral gene marking of bulk cells and subsequent Southern Blot analyses to assess clonal hematopoietic contributions [1-3]. (Source: Experimental Hematology)
Source: Experimental Hematology - August 8, 2018 Category: Hematology Authors: Tobias Maetzig, Michael Morgan, Axel Schambach Tags: Review Source Type: research

Germline Mutations in the Bone Marrow Microenvironment and Dysregulated Hematopoiesis
The relationship between the hematopoietic stem cell (HSC) population and its surrounding bone marrow microenvironment, generally thought of as a collection of functional “niches,” is a rapidly evolving area of research. Gains and losses of function within the microenvironment compartment have been repeatedly linked to leukemic and myelodysplastic conditions affecting adjacent HSCs or more differentiated marrow progenitor cells. In this review, we discuss the int eractions between HSCs and the marrow microenvironment in hematopoietic dysfunction and chemotherapy resistance as well as the therapeutic implication...
Source: Experimental Hematology - August 1, 2018 Category: Hematology Authors: Lane H Miller, Cheng-Kui Qu, Melinda Pauly Tags: Review Source Type: research

Crosstalk between bcr-abl and protease-activated receptor 1 (par1) suggests a novel target in chronic myeloid leukemia
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome (Ph) and the BCR-ABL1 oncogene [1]. This gene encodes the chimeric BCR-ABL oncoprotein, which has constitutive kinase activity and is responsible for the malignant phenotype of leukemic cells [2-3]. Activation of various signaling pathways by BCR-ABL can lead to the malignant transformation of cells by interfering with basic cellular processes, such as cell proliferation, differentiation, adhesion and survival [4-5]. (Source: Experimental Hematology)
Source: Experimental Hematology - August 1, 2018 Category: Hematology Authors: Camilla de S. Borges, Aline F. Ferreira, Vitor H. Almeida, Fausto G. Gomes, Maria Gabriela Berzoti-Coelho, Maira da Costa Cacemiro, Natalia S. Nunes, Lorena L. Figueiredo-Pontes, Belinda P. Sim ões, Fabíola A. Castro, Robson Q. Monteiro Source Type: research

Philadelphia-Like Acute Lymphoblastic Leukemia: Diagnostic dilemma and management perspectives
Acute lymphoblastic leukemia (ALL) is an aggressive hematologic malignancy treated with intensive chemotherapy[1]. In children ALL therapy was a success story [2], however in adults outcomes remain poor [3]. The poor prognosis of adult-ALL is attributed to the accumulation of poor prognostic features including, but not limited to, the higher frequency of poor-risk genomic subgroups, the lower tolerability to prolonged courses of intensive chemotherapy and the high therapy related mortality after hematopoietic cell transplantation (HCT) [4]. (Source: Experimental Hematology)
Source: Experimental Hematology - August 1, 2018 Category: Hematology Authors: Ahmed Kotb, Riad El Fakih, Amr Hanbali, Yousef Hawsawi, Feras Alfraih, Shahrukh Hashmi, Mahmoud Aljurf Tags: Review Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - July 25, 2018 Category: Hematology Source Type: research

Open access? Widening access to Chimeric Antigen Receptor (CAR) therapy for ALL
Category for table of contents – immunotherapy / gene therapy (Source: Experimental Hematology)
Source: Experimental Hematology - July 20, 2018 Category: Hematology Authors: Dr Sara Ghorashian, Prof Persis Amrolia, Prof Paul Veys Tags: Review Source Type: research

Genetic variants of GCH1 associate with chronic and acute crisis pain in African Americans with sickle cell disease
Sickle cell disease (SCD) affects millions of individuals worldwide, including about 100,000 Americans [1, 2]. It is an autosomal recessive disorder where a single nucleotide mutation of the beta-globin gene causes the deoxygenated form of hemoglobin to polymerize. This results in rigid, sickle-shaped red blood cells that aggregate and occlude microvasculature. Consequently, blood flow to organs is obstructed culminating in frequent episodes of severe acute pain, also referred to as acute crisis pain [3, 4]. (Source: Experimental Hematology)
Source: Experimental Hematology - July 19, 2018 Category: Hematology Authors: Nilanjana Sadhu, Ellie H. Jhun, Yingwei Yao, Ying He, Robert E. Molokie, Diana J. Wilkie, Zaijie Jim Wang Source Type: research

Inverse and correlative relationships between TRIBBLES genes indicate non-redundant functions during normal and malignant haemopoiesis
TRIBBLES proteins are pseudokinases that bind and modulate the activity of several signalling molecules, including kinases, phosphatases, transcription factors and components of the ubiquitin proteasome system. From their first identification in mammalian cells, TRIBBLES have been recognised as inducible genes, modulated by a wide range of mitogens and stressors, and associated with downstream regulation of key signalling pathways, including those of AKT, ATF4, NF-kB and MAPKs [1-3]. TRIBBLES pseudokinases are involved in different disease pathways and in many cancer types, including solid tumours, such as melanoma, liver ...
Source: Experimental Hematology - July 19, 2018 Category: Hematology Authors: Mara Salom é, Lisa Hopcroft, Karen Keeshan Source Type: research

Functional Analysis of Fanconi Anemia Mutations in China
Fanconi anemia (FA) is a genetically and phenotypically heterogeneous condition characterized by progressive bone marrow failure (BMF) during childhood, congenital abnormalities, and increased cancer susceptibility. FA is a rare disease with an estimated incidence of 1 –5 in 1,000,000 live births [1, 2]. To date, 22 FANC genes have been identified, including 18 well-known bona fide FA genes (FANC-A, B, C, D1, D2, E, F, G, I, J, L, N, P, Q, T, U,V, W), and 4 FA-like genes (FANC-M, O, R, and S) [3-9]. (Source: Experimental Hematology)
Source: Experimental Hematology - July 18, 2018 Category: Hematology Authors: Niu Li, Lixia Ding, Benshang Li, Jian Wang, Alan D. D'Andrea, Jing Chen Source Type: research

Bone Marrow Eosinophils in Plasma Cell Disorders
Experimental data indicate that eosinophils are of importance for the survival, proliferation and retention of plasma cells (PCs) in the bone marrow (BM) and that they tend to accumulate in the same BM niches [1-3]. Eosinophils might function as antigen-presenting cells (APCs) [4, 5] and are shown to have immunomodulatory properties that could affect tumor growth [6-8]. Recently, Lingblom et  al found a subset of “regulatory eosinophils” with T cell suppressive effect mediated by the protein galectin-10 [9]. (Source: Experimental Hematology)
Source: Experimental Hematology - July 5, 2018 Category: Hematology Authors: Stina Wichert, Åsa Pettersson, Thomas Hellmark, Åsa Johansson, Markus Hansson Tags: Brief Communication Source Type: research

Protagonist or antagonist? The complex roles of retinoids in the regulation of hematopoietic stem cells and their specification from pluripotent stem cells
Hematopoietic stem cells (HSCs) are multipotent cells responsible for the maintenance of the hematopoietic system throughout an individual's life, creating billions of new red blood cells every day [1]. Homeostasis requires maintaining a precise balance between sustaining the HSC population via self-renewal, cell death decisions via apoptosis or senescence and differentiation into increasingly mature progenitors that can give rise to all blood cell lineages [2]. Dysregulation of the careful balance between these cell fate decisions can have deleterious consequences, such as bone marrow failure due to insufficient self-rene...
Source: Experimental Hematology - July 4, 2018 Category: Hematology Authors: Clea S. Grace, Hanna K.A. Mikkola, Diana R. Dou, Vincenzo Calvanese, Roger E. Ronn, Louise E. Purton Tags: Review Source Type: research

Marking of definitive HSC precursors in E7.5 –E8.5 embryos using an Abcg2-CreER lineage-tracing mouse model
Abcg2 is a plasma membrane transporter that is expressed in the side population cells of a variety of tissues, including cancer cells, and is required for their SP phenotype [1,2]. In adult mice, virtually all hematopoietic stem cells (HSCs) express Abcg2 [3]. Lineage-tracing studies using an Abcg2CreERRosaYFP allele in the adult mice confirmed expression of Abcg2 in adult HSCs and revealed that adult tissue-specific intestinal stem cells and spermatogonial stem cells also express Abcg2 [4]. Definitive HSCs (dHSCs) have been identified at embryonic day 10.5 (E10.5) in the midgestation dorsal aorta with an estimated total o...
Source: Experimental Hematology - July 2, 2018 Category: Hematology Authors: Soghra Fatima, Sheng Zhou, Brian P. Sorrentino Tags: Brief Communication Source Type: research

Marking of definitive HSC precursors in E7.5-E8.5 embryos using an Abcg2-CreER lineage tracing mouse model
Abcg2 is a plasma membrane transporter that is expressed in the side population cells of a variety of tissues, including cancer cells, and is required for their SP phenotype [1,2]. In adult mice, virtually all hematopoietic stem cells (HSCs) express Abcg2 [3]. Lineage-tracing studies using an Abcg2CreERRosaYFP allele in the adult mice confirmed expression of Abcg2 in adult HSCs and revealed that adult tissue-specific intestinal stem cells and spermatogonial stem cells also express Abcg2 [4]. Definitive HSCs (dHSCs) have been identified at embryonic day E10.5 in the mid-gestation dorsal aorta with an estimated total of less...
Source: Experimental Hematology - July 2, 2018 Category: Hematology Authors: Soghra Fatima, Sheng Zhou, Brian P. Sorrentino Tags: Brief Communication Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - July 1, 2018 Category: Hematology Source Type: research

Circulating tumor DNA in blood: Future genomic biomarkers for cancer detection
If complexity is defined, cancer is at the top hits. In 2012, 8.2 million reported deaths and 14 million new cases of cancer illustrate that it is the primary cause of mortality and morbidity around the globe. This number is expected to rise by 70% in the next 20 years which is an alarming situation [1-3]. Approximately 90% of cancer associated mortality is caused by metastasis. Metastasis is a process in which cells from the primary tumor mass move to the distant site where they proliferate and form secondary tumor. (Source: Experimental Hematology)
Source: Experimental Hematology - June 23, 2018 Category: Hematology Authors: Sumbal Sumbal, Aneeqa Javed, Bakht Afroze, Hafiza Fizzah Zulfiqar, Faqeeha Javed, Sobia Noreen, Bushra Ijaz Source Type: research

Establishment of a cell model of X-linked sideroblastic anemia using genome editing
Loss-of-function mutation of the ALAS2 gene causes X-linked sideroblastic anemia (XLSA), and a number of missense or nonsense mutations of the ALAS2 gene have been reported to date as a cause of XLSA [1,2]. Although the presence of ring sideroblasts in bone marrow is a critical criterion for the diagnosis of sideroblastic anemia [3], it is still largely unknown how erythroblasts change to sideroblasts in a patient's bone marrow. It has been suggested that an excess of iron, which is not used for heme formation by ferrochelatase, accumulates in the mitochondrial matrix of erythroid precursor cells in patients with XLSA [4],...
Source: Experimental Hematology - June 13, 2018 Category: Hematology Authors: Kiriko Kaneko, Yoshiko Kubota, Kazumi Nomura, Haruka Hayashimoto, Taisei Chida, Naoto Yoshino, Marina Wayama, Katsutoshi Ogasawara, Yukio Nakamura, Ikuo Tooyama, Kazumichi Furuyama Source Type: research

A transcriptomic signature predicting septic outcome in patients undergoing autologous stem cell transplantation
Auto-HSCT is based on the administration of myelosuppressive high-dose chemotherapy, followed by infusion of autologous hematopoietic stem cells to obtain hematologic reconstitution. Hematopoietic stem cells (HSCs) infusion reduces chemotherapy-induced myelosuppression period and procedure-related mortality rate below 3% [1 –3]. With few exceptions (solid tumors, autoimmune diseases), auto-HSCT is essentially indicated for selected hematological malignancies and considered as a standard treatment in young patients with MM and for relapsed or refractory lymphoma. (Source: Experimental Hematology)
Source: Experimental Hematology - June 7, 2018 Category: Hematology Authors: Labiad Yasmine, Venton Geoffroy, Farnault Laure, Baier C éline, Colle Julien, Mercier Cedric, Ivanov Vadim, Nicolino Corinne, Loriod Béatrice, Fernandez-Nunez Nicolas, Torres Magali, Mattei Jean-Camille, Rihet Pascal, Nguyen Catherine, Costello Régis Source Type: research

Prognostic impact of elevated pretreatment serum ferritin in patients with high-risk MDS treated with azacitidine
Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells that mainly affect the elderly and are characterized by ineffective hematopoiesis, leading to cytopenia, infections, and a significant reduction in the quality of life [1,2]. Intensive chemotherapy combined with hematopoietic stem cell transplantation (HSCT) is the only curative treatment for this disease. However, its applicability in elderly patients is limited by comorbidities and poor performance status. Azacytidine (AZA) significantly reduces transfusion dependence, decreases the risk of transformation to acute myeloid leukemia (AML), and...
Source: Experimental Hematology - June 5, 2018 Category: Hematology Authors: Kamel Laribi, Delphine Bolle, Mustapha Alani, Habib Ghnaya, Saga Le Bourdelles, Anne Besan çon, Jonathan Farhi, Nathalie Denizon, Alix Baugier de Materre Tags: Brief Communication Source Type: research

Prognostic impact of elevated pre-treatment serum ferritin in patients with high risk MDS treated with Azacitidine
Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells that mainly affect the elderly, characterized by ineffective hematopoiesis, leading to cytopenia, infections, and a significant reduction in the quality of life [1,2]. Intensive chemotherapy combined with hematopoietic stem cell transplantation (HSCT) is the only curative treatment for this disease. However, it's applicability in elderly patients is limited by comorbidities and poor performance status. Azacytidine (AZA) significantly reduces transfusion dependence, decreases the risk of transformation to acute myeloid leukemia (AML), and impro...
Source: Experimental Hematology - June 5, 2018 Category: Hematology Authors: Kamel Laribi, Delphine Bolle, Mustapha Alani, Habib Ghnaya, Saga Le Bourdelles, Anne Besan çon, Jonathan Farhi, Nathalie Denizon, Alix Baugier de Materre Tags: Brief Communication Source Type: research

Application of small molecule CHIR99021 leads to the loss of hemangioblast progenitor and increased hematopoiesis of human pluripotent stem cells
Hematopoietic differentiation of human pluripotent stem cells (hPSCs) Furthermore, it provides reciprocal knowledge for understanding the hematopoietic specification of various blood lineages [1 –8]. Although the derivation of various types of hematopoietic cells from hPSCs has been achieved, the generation of HSCs remains an ongoing pursuit [9,10]. Because only definitive hematopoiesis generates HSCs, most efforts are directed at enhancing definitive commitment. The embryonic origin of p rimitive and definitive hematopoiesis has been widely discussed and reviewed [11,12]. (Source: Experimental Hematology)
Source: Experimental Hematology - June 4, 2018 Category: Hematology Authors: Yekaterina Galat, Irina Elcheva, Svetlana Dambaeva, Dimantha Katukurundage, Kenneth Beaman, Philip M. Iannaccone, Vasiliy Galat Source Type: research

“Application of Small Molecule CHIR99021 Leads to the Loss of Hemangioblast Progenitor and Increased Hematopoiesis of Human Pluripotent Stem Cells”
Hematopoietic differentiation of human pluripotent stem cells (hPSCs) Furthermore, it provides reciprocal knowledge for understanding the hematopoietic specification of various blood lineages [1-8]. Although the derivation of various types of hematopoietic cells, from hPSC has been achieved, generation of HSCs remains an ongoing pursuit [9, 10]. Because only definitive hematopoiesis generates HSC, most efforts are directed to enhance the definitive commitment. The embryonic origin of primitive and definitive hematopoiesis has been widely discussed, reviewed [11, 12]. (Source: Experimental Hematology)
Source: Experimental Hematology - June 4, 2018 Category: Hematology Authors: Yekaterina Galat, Irina Elcheva, Svetlana Dambaeva, Dimantha Katukurundage, Kenneth Beaman, Philip M. Iannaccone, Vasiliy Galat Source Type: research

Hemoglobin disorders: lentiviral gene therapy in the starting blocks to enter clinical practice
The β-hemoglobinopathies, β-thalassemia (β-thal) and sickle cell disease (SCD), are the most common monogenic diseases worldwide. They result from mutations in the β-globin (HBB) gene locus that lead to the production of insufficient (β0, β+) or aberrant (βS) β-globin protein. (Source: Experimental Hematology)
Source: Experimental Hematology - May 26, 2018 Category: Hematology Authors: Karine Sii-Felice, Marie Giorgi, Philippe Leboulch, Emmanuel Payen Source Type: research

Hematopoietic stem cell fate through metabolic control
Stem cells are self-renewing, and either multi- or unipotent [1-5], and these unique capacities offer opportunities for stem cell-based therapies in the clinic [6]. Past research has implied only limited contributions by hematopoietic stem cells (HSCs) to unperturbed hematopoiesis, but HSCs are still believed essential to hematopoiesis under stress conditions such as hematopoietic recovery [7 –11]. HSC transplantation has therefore been a key therapeutic strategy in combatting hematological disorders [12–14]. (Source: Experimental Hematology)
Source: Experimental Hematology - May 25, 2018 Category: Hematology Authors: Kyoko Ito, Keisuke Ito Source Type: research

Long-term follow-up of de novo chronic phase chronic myelogenous leukemia patients on front-line imatinib
Tyrosine kinase inhibitors (TKIs) have considerably improved the survival of chronic myelogenous leukemia (CML) patients, especially those in chronic phase (CP). TKIs seem to fully eradicate the disease only in a minority of patients, and the majority need to take these drugs over time, probably indefinitely. The firstCP patients exposed to imatinib mesylate (IM) as first-line therapy have been treated since 2000 in the IRIS (International Randomized Study of Interferon and STI571) study [1, 2]. (Source: Experimental Hematology)
Source: Experimental Hematology - May 22, 2018 Category: Hematology Authors: Franck Emmanuel Nicolini, Vincent Alcazer, Pascale Cony-Makhoul, Ma ël Heiblig, Stéphane Morisset, Gaëlle Fossard, Audrey Bidet, Anna Schmitt, Mohamad Sobh, Sandrine Hayette, François-Xavier Mahon, Stéphanie Dulucq, Gabriel Etienne Source Type: research

Long-term follow-up of de novo chronic phase chronic myelogenous leukemia patients on imatinib first-line
Tyrosine kinase inhibitors (TKI) have considerably improved the survival of chronic myelogenous leukemia (CML) patients, especially in chronic phase (CP). TKI seem to fully eradicate the disease only in a minority of patients, and the majority need to take these drugs over time, probably indefinitely. The first CP patients exposed to Imatinib Mesylate (IM), as first-line therapy, have been treated since 2000 in the IRIS study1,2. IM was commercialized in 2001, initially in interferon-resistant and/or -intolerant CP CML patients, and then in first-line in 2003. (Source: Experimental Hematology)
Source: Experimental Hematology - May 22, 2018 Category: Hematology Authors: Franck Emmanuel Nicolini, Vincent Alcazer, Pascale Cony-Makhoul, Ma ël Heiblig, Stéphane Morisset, Gaëlle Fossard, Audrey Bidet, Anna Schmitt, Mohamad Sobh, Sandrine Hayette, François-Xavier Mahon, Stéphanie Dulucq, Gabriel Etienne Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - May 18, 2018 Category: Hematology Source Type: research

The RNA binding protein Ars2 supports hematopoiesis at multiple levels
Arsenic resistance protein 2 (Ars2) is an essential, highly conserved protein with mammals sharing more than 98% amino acid identity [1]. Ars2 was initially described as a modulator of arsenic sensitivity in a cDNA screen [2]; subsequent analysis determined that the ability of Ars2 to modulate arsenic sensitivity likely resulted from a dominant-negative effect of the partial cDNA sequence used in the screen [3]. Full length Ars2 did not impart arsenic resistance, but rather was found to be a component of the 5 ’-7-methylguanosine (7mG) cap binding complex (CBC) that coordinated RNA polymerase II (RNAPII) transcriptio...
Source: Experimental Hematology - May 15, 2018 Category: Hematology Authors: Seerat Elahi, Shawn M. Egan, G. Aaron Holling, Rachel L. Kandefer, Michael J. Nemeth, Scott H. Olejniczak Source Type: research

Mesenchymal stromal cells induce a permissive state in the bone marrow that enhances G-CSF-induced hematopoietic stem cell mobilization in mice
Hematopoietic stem cells (HSC) replenish the peripheral blood (PB) cell pool throughout life. During homeostasis, the vast majority of HSC reside in specialized niches, located in the perivascular area of the trabeculated region of the bone marrow (BM). This HSC microenvironment regulates self-renewal, cell cycle entry and differentiation of HSC and consists of a complex network of hematopoietic and non-hematopoietic cells. (reviewed in [1,2]). (Source: Experimental Hematology)
Source: Experimental Hematology - May 15, 2018 Category: Hematology Authors: Evert-Jan F.M. de Kruijf, Rob Zuijderduijn, Marjolein C. Stip, Willem E. Fibbe, Melissa van Pel Source Type: research

Clonal expansion and myeloid leukemia progression modeled by multiplex gene editing of murine hematopoietic progenitor cells
Recent advances in next-generation sequencing have identified novel mutations and revealed complex genetic architectures in human hematological malignancies. Moving forward, new methods to quickly generate animal models that recapitulate the complex genetics of human hematological disorders are needed to transform the genetic information to new therapies. Here, we used a ribonucleoprotein-based CRISPR/Cas9 system to model human clonal hematopoiesis of indeterminate potential and acute myeloid leukemia (AML). (Source: Experimental Hematology)
Source: Experimental Hematology - May 8, 2018 Category: Hematology Authors: Xiangguo Shi, Ayumi Kitano, Yajian Jiang, Victor Luu, Kevin A. Hoegenauer, Daisuke Nakada Source Type: research

Experimental and integrative analyses identify an ETS1 network downstream of BCR-ABL in chronic myeloid leukemia (CML)
Chronic myeloid leukemia (CML) accounts for approximately 15% of newly diagnosed cases of leukemia in adults [1]. The BCR-ABL1 fusion gene resulting from the t(9;22) chromosomal translocation is expressed in all CML cells. It encodes the BCR-ABL protein, which is required for oncogenic transformation [2,3]. BCR-ABL is a constitutively active tyrosine kinase that promotes the proliferation and survival of leukemic cells through several downstream well-known effectors such as RAS, MYC, and STAT [4 –6]. (Source: Experimental Hematology)
Source: Experimental Hematology - May 4, 2018 Category: Hematology Authors: Christophe Desterke, Maud Voldoire, Marie-Laure Bonnet, Nathalie Sorel, Sarah Pagliaro, Hind Rahban, Annelise Bennaceur-Griscelli, Emilie Cayssials, Jean-Claude Chomel, Ali G. Turhan Source Type: research

Experimental and integrative analyses identify an ETS1 network downstream BCR-ABL in chronic myeloid leukemia (CML)
Chronic myeloid leukemia (CML) accounts for approximately 15% of the newly diagnosed cases of leukemia in adults (1). The BCR-ABL1 fusion gene resulting from the t (9;22) chromosomal translocation is expressed in all CML cells. It encodes the BCR-ABL protein, which is required for oncogenic transformation (2,3). BCR-ABL is a constitutively active tyrosine kinase that promotes the proliferation and survival of leukemic cells through several downstream well-known effectors such as RAS, MYC, and STAT (4 –6). (Source: Experimental Hematology)
Source: Experimental Hematology - May 4, 2018 Category: Hematology Authors: Christophe Desterke, Maud Voldoire, Marie-Laure Bonnet, Nathalie Sorel, Sarah Pagliaro, Hind Rahban, Annelise Bennaceur Griscelli, Emilie Cayssials, Jean-Claude Chomel, Ali G Turhan Tags: Malignant Hematopoiesis Source Type: research

RUNX1 promotes cell growth in human T-cell acute lymphoblastic leukemia by transcriptional regulation of key target genes
The RUNX1 gene, a member of the RUNT-related transcription factor family, is dysregulated in many types of hematologic malignancy [1]. It was first identified as a partner with ETO in t(8;21) acute myelogenous leukemia (AML), and later with TEL/ETV6 in t(12;21) B-lineage acute lymphoblastic leukemia and with EVI1/MECOM in t(3;21) therapy-related AML/myelodysplastic syndrome (MDS). Point mutations and small indels in RUNX1 have been described in MDS/AML and familial platelet disorder with associated myeloid malignancy [2] and more recently in T-cell acute lymphoblastic leukemia (T-ALL) [3 –6]. (Source: Experimental Hematology)
Source: Experimental Hematology - May 4, 2018 Category: Hematology Authors: Catherine E. Jenkins, Samuel Gusscott, Rachel J. Wong, Olena O. Shevchuk, Gurneet Rana, Vincenzo Giambra, Kateryna Tyshchenko, Rashedul Islam, Martin Hirst, Andrew P. Weng Tags: Malignant Hematopoiesis Source Type: research

Hematopoietic insults damage bone marrow niche by activating p53 in vascular endothelial cells
During the lifetime of an animal, hematopoietic stem cells (HSCs) are exposed to various insults, such as genotoxic stress, inflammation, and infection, which directly affect HSCs. These insults deplete HSCs and cause a functional decline in HSCs, and also promote their aging and transformation [1 –3]. However, the impact of hematopoietic insults on niche cells remains largely unknown. (Source: Experimental Hematology)
Source: Experimental Hematology - April 27, 2018 Category: Hematology Authors: Sha Si, Yaeko Nakajima-Takagi, Takahito Iga, Mayoko Tsuji, Libo Hou, Motohiko Oshima, Shuhei Koide, Atsunori Saraya, Satoshi Yamazaki, Keiyo Takubo, Yoshiaki Kubota, Tohru Minamino, Atsushi Iwama Tags: Regular article Source Type: research

Aberrant determination of phenotypic markers in chronic lymphocytic leukemia (CLL) lymphocytes after cryopreservation
In a diagnostic setting, quantifying the expression of membrane proteins by flow cytometry is generally performed using fresh blood samples, in which the conformation of the epitope is likely to be in its native form. However, in a research environment, cells such as peripheral blood mononuclear cells (PBMCs) are often cryopreserved in liquid nitrogen and analyzed as needed. Cryogenic preservation requires the addition of cryoprotective reagents, most commonly dimethyl sulfoxide (DMSO), to protect the cells from damage during the preservation process [1]. (Source: Experimental Hematology)
Source: Experimental Hematology - April 26, 2018 Category: Hematology Authors: Lauren A. Thurgood, Karen M. Lower, Cindy Macardle, Bryone J. Kuss Tags: Brief Communications Source Type: research

Aberrant detection of phenotypic markers in chronic lymphocytic leukemia (CLL) lymphocytes after cryopreservation
In a diagnostic setting, quantifying the expression of membrane proteins by flow cytometry is generally performed using fresh blood samples, in which the conformation of the epitope is likely to be in its native form. However, in a research environment, cells such as peripheral blood mononuclear cells (PBMCs) are often cryopreserved in liquid nitrogen and analyzed as needed. Cryogenic preservation requires the addition of cryoprotective reagents, most commonly dimethyl sulfoxide (DMSO), to protect the cells from damage during the preservation process [1]. (Source: Experimental Hematology)
Source: Experimental Hematology - April 26, 2018 Category: Hematology Authors: Lauren A. Thurgood, Karen M. Lower, Cindy Macardle, Bryone J. Kuss Tags: Brief Communications Source Type: research

Aberrant detection of phenotypic markers in chronic lymphocytic leukemia (CLL) lymphocytes following cryopreservation
In a diagnostic setting, quantifying the expression of membrane proteins by flow cytometry is generally carried out using fresh blood samples where the conformation of the epitope is likely to be in its native form. However, in a research environment, cells such as peripheral blood mononuclear cells (PBMCs) are often cryopreserved in liquid nitrogen and analysed as needed. Cryogenic preservation requires the addition of cryoprotective reagents, most commonly, dimethyl sulfoxide (DMSO), in order to protect the cells from damage during the preservation process1. (Source: Experimental Hematology)
Source: Experimental Hematology - April 26, 2018 Category: Hematology Authors: Lauren A. Thurgood, Karen M. Lower, Cindy Macardle, Bryone J. Kuss Tags: Brief Communication Source Type: research

Branched-chain amino acid depletion conditions bone marrow for hematopoietic stem cell transplantation avoiding amino acid imbalance-associated toxicity
Bone marrow (BM) or hematopoietic stem cell (HSC) transplantation (HSCT) is a potentially curative treatment for a range of hematological disorders, such as immunodeficiency diseases (Copelan,  2006). However, “space” within the recipient's HSC niche (Morrison and Scadden, 2014, Boulais and Frenette, 2015) must be first made to allow donor HSCs to engraft (Czechowicz et al., 2007). Unfortunately, morbidity and mortality associated with traditional BM conditioning regimens, radiatio n and/or chemotherapy, currently limit the application of HSCT (Gyurkocza and Sandmaier, 2014). (Source: E...
Source: Experimental Hematology - April 26, 2018 Category: Hematology Authors: Adam C Wilkinson, Maiko Morita, Hiromitsu Nakauchi, Satoshi Yamazaki Tags: Brief Communication Source Type: research

Elevated serum BDNF levels are associated with favorable outcome in CLL patients: Possible link to CXCR4 downregulation
CXCR4 is an important and broadly expressed chemokine receptor that is involved in neuronal and hematopoietic cell migration [1]. The well-known ligand for CXCR4, Stromal Derived Factor-1 (SDF1), is a potent chemoattractant that is constitutively expressed by fibroblastic stromal cells and regulates lymphocyte trafficking and extravasation of mononuclear cells [2]. Chronic lymphocytic leukemia (CLL) cells were previously shown to overexpress CXCR4 [3]. Overexpression of CXCR4 in CLL cells was suggested to increase avidity and tropism of the malignant cells to the hematopoietic and lymphatic tissues, leading to lymph node a...
Source: Experimental Hematology - April 26, 2018 Category: Hematology Authors: David Azoulay, Yair Herishanu, Mika Shapiro, Yarden Brenshaft, Celia Suriu, Luiza Akria, Andrei Braester Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - April 25, 2018 Category: Hematology Source Type: research

Synergistic action of dual IGF1/R and MEK inhibition sensitizes childhood acute lymphoblastic leukemia (ALL) cells to cytotoxic agents and involves downregulation of STAT6 and PDAP1
Although cure rates for childhood acute lymphoblastic leukemia (ALL) have increased dramatically over recent years through the integration of risk stratification into treatment protocols [1 –3], failure of remission-inducing therapy is associated with only a 30% 10-year survival rate [4] and relapsed ALL remains the most common cause of cancer-related death in children [5–7]. There is a need for new therapeutic approaches with minimal toxicities for higher-risk leukemias. (Source: Experimental Hematology)
Source: Experimental Hematology - April 12, 2018 Category: Hematology Authors: Victoria J. Weston, Wenbin Wei, Tatjana Stankovic, Pamela Kearns Source Type: research

Synergistic Action of Dual IGF1/R and MEK Inhibition Sensitizes Childhood Acute Lymphoblastic Leukaemia (ALL) Cells to Cytotoxic Agents and Involves Down-Regulation of STAT6 and PDAP1
Although cure rates for childhood ALL have increased dramatically over recent years through the integration of risk-stratification into treatment protocols [1-3], failure of remission-inducing therapy is associated with only a 30% ten-year survival rate [4] and relapsed ALL remains the commonest cause of cancer-related death in children [5-7]. There is a need for new therapeutic approaches with minimal toxicities for higher-risk leukaemias. (Source: Experimental Hematology)
Source: Experimental Hematology - April 12, 2018 Category: Hematology Authors: Victoria J Weston, Wenbin Wei, Tatjana Stankovic, Pamela Kearns Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - April 11, 2018 Category: Hematology Source Type: research

The physical and cellular conditions of the human pulmonary circulation enable thrombopoiesis
Thrombopoiesis is the biological process dedicated to the production of functional platelets by their precursors, megakaryocytes (MKs). During their maturation in the bone marrow (BM), MKs migrate to the vascular niche [1], but the final maturation step that involves the process of platelet release is not fully documented in human physiology [2]. (Source: Experimental Hematology)
Source: Experimental Hematology - April 11, 2018 Category: Hematology Authors: Yasmine Ouzegdouh, Claude Capron, Thomas Bauer, Etienne Puymirat, Jean-Luc Diehl, John F. Martin, Elisabeth Cramer-Bord é Tags: Brief Communication Source Type: research

The physical and cellular conditions of the human pulmonary circulation, enable thrombopoesis#
Thrombopoiesis is the biological process dedicated to the production of functional platelets by their precursors, megakaryocytes (MKs). During their maturation in the bone marrow (BM), MKs migrate to the vascular niche [2] but the final maturation step which involves the process of platelet release is not fully documented in human physiology [1] (Source: Experimental Hematology)
Source: Experimental Hematology - April 11, 2018 Category: Hematology Authors: Yasmine Ouzegdouh, Claude Capro n, Thomas Bauer, Etienne Puymirat, Jean-Luc Diehl, John F . Martin, Elisabeth Cramer-Bord é Source Type: research

Harnessing the potential of epigenetic therapies for childhood acute myeloid leukemia
Acute myeloid leukemia (AML) results from clonal expansion of primitive myeloid cells that are incapable of differentiation. These clones have acquired genetic and epigenetic alterations that cause uncontrolled proliferation at the expense of normal hematopoiesis, leading to bone marrow exhaustion. The recent identification and characterization of many of these alterations [1] create the opportunity for the development of targeted treatments. Cancer genome consortiums have identified genes commonly mutated in AML, many of which are associated with epigenetic regulation [2 –5], indicating that chromatin modifiers play...
Source: Experimental Hematology - March 30, 2018 Category: Hematology Authors: Ashley A. Newcombe, Brenda E.S. Gibson, Karen Keeshan Tags: Review Source Type: research

Harnessing the potential of epigenetic therapies for childhood AML
• Overview of the major epigenetic mutations and mechanisms contributing to paediatric and adult AML• Summary of different clinical trials with epigenetic implications in paediatric and adult AML• Rationale for epigenetic therapies in AML (Source: Experimental Hematology)
Source: Experimental Hematology - March 30, 2018 Category: Hematology Authors: Ashley A. Newcombe, Brenda E.S Gibson, Karen Keeshan Tags: Review Source Type: research