An evolving technology for an evolving disease: A commentary on NGS-based MRD evaluation in B-ALL
The ability to detect “minimal residual disease” (MRD) is profoundly impacting the treatment approach to acute lymphoblastic leukemia (ALL). While several MRD assays are available, including flow cytometry and targeted PCR, “high throughput sequencing” (HTS) or next generation sequencing (NGS) methods appear part icularly promising. One of these approaches – the Adaptive Biotechnologies clonoSEQ® assay – was recently granted FDA approval. No published trial tells us what to do with knowledge of NGS-based MRD status, but clearly this is the next step. (Source: Leukemia Research)
Source: Leukemia Research - November 16, 2018 Category: Hematology Authors: Carol Fries, Richard Burack Tags: Commentary Source Type: research
Anatomical Site as a Parameter in the Predictive Model of Diffuse Large B Cell Lymphoma
Classification is essentially about prediction. Being a member of a class connotes specific qualities that are characteristic of class membership. We rely on classification to inform our thoughts and expectations. (Source: Leukemia Research)
Source: Leukemia Research - November 14, 2018 Category: Hematology Authors: David Kaplan Tags: Commentary Source Type: research
A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients
Several clinical and biological features, like cytogenetic and molecular alterations, may predict the short- and long-term outcomes in patients with AML treated with intensive approaches [1,2]. However, the main prognostic factor after front-line induction treatment is the leukemic cell sensitivity to the chemotherapy itself (i.e, to achieve or not a first CR as well as the quality and duration of the CR) [3,4]. In order to predict response to chemotherapy, many individualized sensitivity and resistance assays have been deployed for detecting ex vivo drug-inducible cell death. (Source: Leukemia Research)
Source: Leukemia Research - November 13, 2018 Category: Hematology Authors: David Mart ínez-Cuadrón, Cristina Gil, Josefina Serrano, Gabriela Rodríguez, Jaime Pérez-Oteyza, Raimundo García-Boyero, Santiago Jiménez-Bravo, Susana Vives, María Belén Vidriales, Esperanza Lavilla, José A. Pérez-Simón, Mar Tormo, Mercedes Co Source Type: research
Allogeneic hematopoietic stem cell transplantation for the treatment of BCR-ABL1-negative atypical chronic myeloid leukemia and chronic neutrophil leukemia: a retrospective nationwide study in Japan
Atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) are BCR-ABL1 fusion gene-negative myeloid neoplasms with an elevated number of neutrophils [1]. Both diseases are very rare; there have been only a few cohorts of aCML patients reported, with the largest case series consisting of 65 patients [2,3], and only approximately 150 CNL cases have been reported to date [4]. Both diseases have the overlapping clinical manifestations, such as leukocytosis, bleeding diathesis, and splenomegaly [5 –11]; and share the oncogenic-drivers and disease-modifying mutations with other myeloid neoplasms (e.g. (S...
Source: Leukemia Research - November 12, 2018 Category: Hematology Authors: Hidehiro Itonaga, Shuichi Ota, Takashi Ikeda, Hirohumi Taji, Itsuto Amano, Yuichi Hasegawa, Tatsuo Ichinohe, Takahiro Fukuda, Yoshiko Atsuta, Akihiko Tanizawa, Takeshi Kondo, Yasushi Miyazaki Tags: Research paper Source Type: research
Systemic lupus erythematosus and lymphoma: Incidence, pathogenesis and biology
Systemic lupus erythematosus (SLE) is a multisystem auto-immune inflammatory disease, with prevalence ranging from 20-150 cases per 100,000 population [1]. It mostly affects women of childbearing age and can involve any vital organ, in particular brain, kidneys, skin, heart and blood. SLE shows diversity, ranging from mild to potentially fatal disease mostly due to end stage organ damage [1]. In addition to classical clinical manifestations, SLE may also present with associated co-morbidities, most significantly cardiovascular disease with accelerated atherosclerosis [2]. (Source: Leukemia Research)
Source: Leukemia Research - November 12, 2018 Category: Hematology Authors: Alina Klein, Aaron Polliack, Anat Gafter-Gvili Source Type: research
Novel therapeutics in the treatment of hairy cell leukemia variant
Hairy cell leukemia variant (vHCL) is a B-cell lymphoproliferative disorder. The 2016 US lymphoid malignancy statistics estimate that vHCL was diagnosed in 810 patients, with an age adjusted US standard population incidence of approximately 0.2 per 100,000 [1]. Prior to 2008, when the World Health Organization classified vHCL as a provisional diagnosis, hairy cell leukemia encompassed both classic hairy cell leukemia (cHCL) and vHCL. These two entities exhibit unique morphological, cytological and hematologic findings and are not considered to be biologically related. (Source: Leukemia Research)
Source: Leukemia Research - November 5, 2018 Category: Hematology Authors: Paul Letendre, Donald Doll Tags: Letter to the Editor Source Type: research
A clinical perspective on immunoglobulin heavy chain clonal heterogeneity in B cell acute lymphoblastic leukemia
Of the 3,100 children diagnosed with acute lymphoblastic leukemia (ALL) in the U.S. each year [1], approximately 10% will ultimately succumb to their disease [2,3]. Prognosis is far worse for the>3,000 U.S. adults diagnosed annually, with only about 30-40% 5-year overall survival among this cohort [4,5]. Nearly 1 in 10 adults will never even achieve remission, and more than half of those who do will go on to suffer relapse and disease-related mortality [6]. (Source: Leukemia Research)
Source: Leukemia Research - November 3, 2018 Category: Hematology Authors: Carol Fries, W. Richard Burack Source Type: research
LMO2 functional and transcriptional regulatory profiles in hematopoietic cells
The human lmo2 gene was first cloned from acute T lymphocytic leukemia (T-ALL) patients [1,2]. It is expressed in a variety of tissues with the highest in hematopoietic stem/progenitor cells [3]. However, LMO2 expression during thymocyte development was specifically turned off, and ectopic expression of LMO2 caused T-cell development arrest and T cell leukemia [4,5]. LMO2 consists of only two tandem LIM domains, lacks direct DNA-binding capacity and always acts as a bridging or blocking molecular via protein-protein interactions [4,6]. (Source: Leukemia Research)
Source: Leukemia Research - November 2, 2018 Category: Hematology Authors: Chao Wu, Mei Yuan, Yang Gao, Wei Sun Tags: Correspondence Source Type: research
Chemosensitivity is differentially regulated by the SDF-1/CXCR4 and SDF-1/CXCR7 axes in acute lymphoblastic leukemia with MLL gene rearrangements
Rearrangements of the mixed-lineage-leukemia (MLL) gene at chromosome 11q23 are frequently observed in infantile acute lymphoblastic leukemia (ALL) and therapy-related second leukemia [1,2], and ALL with MLL gene rearrangements (MLL+ALL) is refractory to chemotherapy and its prognosis is still dismal although it has been improved to some extent by performing hematopoietic stem cell transplantation [3,4]. Of interest, MLL+ALL has a unique gene profile clearly distinguishable from other types of ALL and acute myeloid leukemia (AML), and specific genes such as Fms-like tyrosine kinase 3 (FLT3), CD44, LMO2, and HOXA9 are overe...
Source: Leukemia Research - November 2, 2018 Category: Hematology Authors: Norie Ando, Yoshiyuki Furuichi, Shin Kasai, Minori Tamai, Daisuke Harama, Keiko Kagami, Masako Abe, Kumiko Goi, Takeshi Inukai, Kanji Sugita Tags: Research paper Source Type: research
Endothelin Receptor Emerges as a Potential Target of Hoxa9-mediated Leukemogenesis
In 2000, Padr ó et al. published a surprising finding -- bone marrow from patients with acute myeloid leukemia (AML) revealed evidence of increased angiogenesis. Microvessels staining positive for thrombomodulin and von Willebrand factor were observed at high density compared to normal bone marrow with evidence of endothelial sprouting and smaller lumens [1]. Unexpected for a liquid tumor, this prompted further inquiry as to whether a vascular niche may be essential to support leukemic cell growth. (Source: Leukemia Research)
Source: Leukemia Research - November 1, 2018 Category: Hematology Authors: Eric Gars, Satinder Kaur, Daniel Thomas Tags: Commentary Source Type: research
Editorial Board
(Source: Leukemia Research)
Source: Leukemia Research - November 1, 2018 Category: Hematology Source Type: research
The predictive value of morphological findings in early diagnosis of acute myeloid leukemia with recurrent cytogenetic abnormalities
Since the introduction of the French-American-British (FAB) morphological system, acute leukemia classifications were traditionally based on quantitative and qualitative evaluation of blast populations in bone marrow [1]. Although revolutionary at that time, particularly in the identification of acute promyelocytic leukemia (APL), the FAB morphological system had poor reproducibility and prognostic value [2,3]. Further developments in the fields of cell immunophenotyping by flow cytometry, cytogenetic and molecular genetic analysis provided new insights into leukemia biology, opening a new era of the integrated diagnostic ...
Source: Leukemia Research - November 1, 2018 Category: Hematology Authors: Ljubomir Jakovic, Andrija Bogdanovic, Vesna Djordjevic, Marija Dencic-Fekete, Nada Kraguljac-Kurtovic, Vesna Knezevic, Natasa Tosic, Sonja Pavlovic, Tatjana Terzic Tags: Research paper Source Type: research
Hydroxyurea prior to intensive chemotherapy in AML with moderate leukocytosis
Hydroxyurea (HU) is an oral anti-proliferative drug that interferes with DNA synthesis by inhibiting ribonucleotide reductase. HU has long been used in acute myeloid leukemia (AML) for cytoreduction as part of best supportive care, or as a prephase before intensive chemotherapy in patients with an elevated white blood cell (WBC) count [1]. A recent retrospective study showed that a pre-treatment with HU prior to intensive chemotherapy could improve short-term survival of patients with hyperleukocytic AML (HL-AML, WBC>50.109/L), but not complete remission (CR) or relapse-free survival (RFS) [2]. (Source: Leukemia Research)
Source: Leukemia Research - October 30, 2018 Category: Hematology Authors: Sarah Bertoli, Suzanne Tavitian, Muriel Picard, Fran çoise Huguet, François Vergez, Eric Delabesse, Audrey Sarry, Emilie Bérard, Christian Récher Tags: Letter to the Editor Source Type: research
Rituximab maintenance in elderly patients with follicular lymphoma
Follicular lymphoma (FL) is a chronic, indolent lymphoid malignancy and represents the most common slow growing lymphoma in the United States and Europe1. Patients with FL experience generally favorable outcomes with median overall survival (OS) lasting close to 18 years2. Improvements in FL survival have occurred consistently over the past several years, and for symptomatic patients treated with chemoimmunotherapy, durable disease control is achievable, lasting several years. Chemo-immunotherapy with antiCD20 antibody rituximab has changed the treatment landscape of FL by improving response rates and progression free surv...
Source: Leukemia Research - October 27, 2018 Category: Hematology Authors: Carla Casulo Source Type: research
MXD1 regulates the imatinib resistance of chronic myeloid leukemia cells by repressing BCR-ABL1 expression
Chronic myeloid leukemia (CML) is a common myeloproliferative neoplasm characterized by the chromosomal translocation t(9;22) (q34;q11) [1]. This translocation causes the generation of a fusion oncogene, namely, the BCR-ABL1 encoding fusion protein with constitutive tyrosine kinase activity, which gives rise to the uncontrolled growth of myeloid cells in the bone marrow through a series of downstream pathways [2,3]. One of the first-line treatments for CML is imatinib, a tyrosine kinase inhibitor (TKI) that competitively binds to the ATP-binding site of Bcr-Abl and blocks the downstream signal pathway [4,5]. (Source: Leukemia Research)
Source: Leukemia Research - October 25, 2018 Category: Hematology Authors: Chen Huan, Lou Jin, Wang Heng, An Na, Pan Yuming, Du Xin, Zhang Qiaoxia Source Type: research
