Final Results of a Randomized Multicenter Phase II Study of Alvocidib, Cytarabine, and Mitoxantrone versus Cytarabine and Daunorubicin (7+3) in Newly Diagnosed High-Risk Acute Myeloid Leukemia (AML)
Despite recent advances in the management of subpopulations of AML, overall outcomes remain unsatisfactory. Encouraging results were seen with alvocidib (formerly known as flavopiridol), a CDK9 inhibitor with pan-cyclin-dependent kinase (CDK) activity, followed by cytarabine and mitoxantrone (FLAM) in serial phase I-II studies in newly diagnosed AML patients [1 –7]. Therefore, we conducted a randomized phase II clinical trial comparing FLAM to cytarabine and daunorubicin (7 + 3) in newly diagnosed AML patients 18-70 years of age with non-favorable risk cytogenetics [8]. (Source: Leukemia Research)
Source: Leukemia Research - August 10, 2018 Category: Hematology Authors: Joshua F. Zeidner, Matthew C. Foster, Amanda L. Blackford, Mark R. Litzow, Lawrence E. Morris, Stephen A. Strickland, Jeffrey E. Lancet, Prithviraj Bose, M. Yair Levy, Raoul Tibes, Ivana Gojo, Christopher D. Gocke, Gary L. Rosner, Richard F. Little, John Tags: Letter to the Editor Source Type: research
Dynamic changes in HLA-DR expression during short-term and long-term ibrutinib treatment in patients with chronic lymphocytic leukemia
Ibrutinib, an irreversible small-molecule inhibitor of both Bruton's tyrosine kinase (BTK) and interleukin-2 inducible kinase (ITK), has shown outstanding efficacy in controlling relapsed/refractory and/or previously untreated CLL [1,2]. Although the exact mechanisms are not completely understood, there is a growing body of evidence about the immunomodulating effects of ibrutinib on different immune cell types and signalling pathways in various types of hematologic and solid cancers [3,4,5]. In CLL, ibrutinib has been shown to abrogate CLL cell trafficking, signalling, and adhesion in response to tissue homing chemokines s...
Source: Leukemia Research - August 10, 2018 Category: Hematology Authors: Gayane Manukyan, Peter Turcsanyi, Zuzana Mikulkova, Gabriela Gabcova, Renata Urbanova, Petr Gajdos, Veronika Smotkova Kraiczova, Sarka Zehnalova, Tomas Papajik, Eva Kriegova Tags: Research paper Source Type: research
Targeting acute myeloid leukemia CD34+ stem/progenitor cells with small molecule inhibitor MK-8776
Standard therapy or improving standard therapy can make the majority of acute myeloid leukemia (AML) patients partly or complete remission. However, the treatment often relapses from remission. A small fraction of leukemic stem cells (LSCs) are responsible for the accumulation of immature malignant cells in the bone marrow. LSCs were considered the ‘bad seeds’, it was showed that AML patients with LSCs enrichment have worse clinical outcomes [1]. Therefore, targeting LSCs by candidate drugs is crucial for AML therapies. (Source: Leukemia Research)
Source: Leukemia Research - August 7, 2018 Category: Hematology Authors: Hu Lei, Li Yang, Li Zhou, Ying Tong, Yingli Wu Tags: Correspondence Source Type: research
Combination of cabazitaxel and plicamycin induces cell death in drug resistant B-cell acute lymphoblastic leukemia
B-cell acute lymphoblastic leukemia (ALL) manifests itself as an accumulation of poorly differentiated malignant lymphoid cells within the bone marrow (BM), resulting in the disruption of normal hematopoiesis [1]. BM is also the most common site of disease relapse, contributed by minimal residual disease (MRD), a major factor associated with poor prognosis and mortality [2]. Unlike T-cell lymphoblastic leukemia, MRD in ALL has been less completely studied and its etiology still remains to be more clearly delineated [3]. (Source: Leukemia Research)
Source: Leukemia Research - August 6, 2018 Category: Hematology Authors: Rajesh R. Nair, Debbie Piktel, Werner J. Geldenhuys, Laura F. Gibson Source Type: research
IRF4 in Multiple Myeloma —biology, disease and therapeutic target
Multiple Myeloma (MM) is an aggressive and incurable cancer characterized by the clonal proliferation of bone marrow plasma cells. MM diagnosis follows the appearance of end-organ damage known as the CRAB criteria (increased calcium level, renal dysfunction, anaemia, and destructive bone lesions) but can also be diagnosed in presence of at least one myeloma defining event or MED (bone marrow plasma cells greater than or equal to 60%; serum free light chain ratio greater than or equal to 100 provided involved FLC level is at least 100 mg/L; more than one focal lesion on magnetic resonance imaging that is at least 5 mm ...
Source: Leukemia Research - August 3, 2018 Category: Hematology Authors: Alessandro Agnarelli, Tim Chevassut, Erika J. Mancini Source Type: research
CC-486 (Oral Azacitidine) in Patients with Myelodysplastic Syndromes with Pretreatment Thrombocytopenia
Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and peripheral cytopenias. Approximately 40% of all MDS patients, and up to 80% of patients with higher-risk MDS, experience thrombocytopenia, which is typically defined as platelet count (Source: Leukemia Research)
Source: Leukemia Research - August 3, 2018 Category: Hematology Authors: Guillermo Garcia-Manero, Bart L. Scott, Christopher R. Cogle, Thomas E. Boyd, Suman Kambhampati, Joel Hetzer, Qian Dong, Keshava Kumar, Stacey M. Ukrainskyj, CL Beach, Barry S. Skikne Source Type: research
Editorial Board
(Source: Leukemia Research)
Source: Leukemia Research - August 1, 2018 Category: Hematology Source Type: research
Secondary Acute Lymphoblastic Leukemia, a retrospective analysis from Washington University and meta-analysis of published data
Secondary malignancies are broadly defined as a group of cancers arising after a previous malignancy and have become increasingly appreciated due to improvement in cancer survival. Therapy-related malignancies are a sub-group of secondary malignancies in which the exposure to prior chemotherapy or radiation therapy is instrumental to the establishment of the secondary cancer. Other than the role of previous therapies, underlying genetic predisposition, immunodeficiency states or simple coincidence have all also been invoked as potential causative factors for the development of secondary cancers [1]. (Source: Leukemia Research)
Source: Leukemia Research - August 1, 2018 Category: Hematology Authors: Francesca Ferraro, Feng Gao, Keith Stockerl-Goldstein, Peter Westervelt, John F. DiPersio, Armin Ghobadi Source Type: research
Notch1 activation enhances proliferation via activation of cdc2 and delays differentiation of myeloid progenitors
The Notch signaling pathway is evolutionally conserved and has crucial roles in the control of proliferation, differentiation, apoptosis, and fate decision in numerous cell types [1,2]. The mammalian Notch family consists of four highly conserved transmembrane receptors (Notch 1, 2, 3, and 4), which can interact with five Notch ligands (Jagged 1 and 2, Delta-like 1, 3, and 4). When activated by ligand binding, the Notch receptor is cleaved, and its intracellular domain (ICN) translocates to the nucleus [3]. (Source: Leukemia Research)
Source: Leukemia Research - July 30, 2018 Category: Hematology Authors: Makoto Nakamura, Lizi Wu, James D. Griffin, Satoru Kojika, Kumiko Goi, Takeshi Inukai, Kanji Sugita Source Type: research
Association of recipient and donor hypercholesterolemia prior allogeneic stem cell transplantation and graft-versus-host disease
Hypercholesterolemia leads to cholesterol accumulation in macrophages and other immune cells, promoting inflammatory responses. Also, signaling from toll-like receptors (TLRs) results in further cholesterol accumulation and increased inflammatory responses as a result of diminished cholesterol efflux, exacerbating chronic metabolic inflammation [1]. Although the links between cholesterol and inflammation are best exemplified by atherosclerosis, similar mechanisms may also contribute to other metabolic disorders such as obesity [2] or to autoimmune diseases. (Source: Leukemia Research)
Source: Leukemia Research - July 30, 2018 Category: Hematology Authors: Monica M. Rivera-Franco, Eucario Le ón-Rodríguez, Isabel K. Lastra German, Andrea A. Mendoza Farias Tags: Research paper Source Type: research
The clinical significance of CDX2 in leukemia: a new perspective for leukemia research
The Caudal-type homeobox gene CDX2 encodes the transcription factor which is implicated in the early stages of embryogenesis and hematopoietic development [1,2]. CDX2 is a part of CDX cluster, known as ParaHox [3]. Previous studies have shown that CDX2 exert its effects by regulating HOX gene expression [4]. The HOX gene clusters are a family of homeodomain-containing transcription factors [5], however, the expression of CDX2 in adults is restricted to intestine and it is not observed in the hematopoietic tissues. (Source: Leukemia Research)
Source: Leukemia Research - July 28, 2018 Category: Hematology Authors: Mina Darvishi, Pargol Mashati, Abbas Khosravi Tags: Review Article Source Type: research
A lower ALC/AMC ratio is associated with poor prognosis of peripheral T-cell lymphoma-not otherwise specified
Peripheral T cell lymphomas (PTCLs) are broadly heterogeneous diseases; however, their prognosis is poorer than B-cell non-Hodgkin lymphomas (NHLs) [1,2]. The prognoses of PTCLs differ according to disease subtype. PTCLs have been classified according to clinical features into four groups using the 2016 World Health Organization (WHO) classification system. These four groups are as follows: peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), angioimmunoblastic T - cell lymphoma (AITL), adult T - cell leukemia/lymphoma (ATLL) and anaplastic large cell lymphoma (ALCL) [3]. (Source: Leukemia Research)
Source: Leukemia Research - July 26, 2018 Category: Hematology Authors: Qian Li, Shuang Gao, Jing Ma, Su Liu, Yuanfang Yue, Lin Chen, Han Li, Xue Wang, Dongying Li, Zeng Cao, Zhigang Zhao, Xiaofang Wang, Yu Yong, Yizhuo Zhang, Yafei Wang Tags: Research paper Source Type: research
The IPSS-R has prognostic impact in untreated patients with MDS del(5q)
Myelodysplastic syndromes (MDS) are known to occur as an insufficiency of the bone marrow to produce a satisfactory amount of mature and functioning blood cells, resulting in cytopenia, especially in anemia in most cases, and dysplasia. MDS del(5q) is a subtype presenting with a deletion in the long arm of chromosome 5, which predominantly occurs in women and clinically presents with prominent anemia, dysmegakaryopoesis, often thrombocytosis and low blast counts in the bone marrow. As transformation rates into acute myeloid leukemia (AML) are relatively low and patients tend to suffer from mild symptoms compared to other s...
Source: Leukemia Research - July 23, 2018 Category: Hematology Authors: J. Kaivers, M. Lauseker, B. Hildebrandt, P. Fenaux, M. Pfeilst öcker, P. Valent, U. Platzbecker, R. Latagliata, E.N. Oliva, B. Xicoy, K. Götze, C. Ganster, D. Haase, G. Bug, A. Kündgen, N. Gattermann, R. Haas, U. Germing Source Type: research
A phase 1 study of chemosensitization with plerixafor plus G-CSF in adults with relapsed acute myeloid leukemia
Sensitization of leukemia cells and their progenitors by granulocytic growth factors may modulate the cell cycle kinetics of blast cells and is a tool to enhance the efficacy of chemotherapy in younger adults with acute myeloid leukemia (AML) [1,2]. Resistance to chemotherapy may be related to the adherence of leukemia cells to the stromal environment via specific receptor and adhesion molecules.In this setting, the CXCR4/SDF-1 axis functions as a main regulator of homing and retention of both normal and malignant hematopoietic cells in the bone marrow (BM) [3]. (Source: Leukemia Research)
Source: Leukemia Research - July 21, 2018 Category: Hematology Authors: Ma ël Heiblig, Mohamed Elhamri, Xavier Thomas, Adriana Plesa, Emmanuel Raffoux, Sandrine Hayette Tags: Letter to the Editor Source Type: research
Non-internal tandem duplication (ITD), non-tyrosine kinase domain (TKD) FLT3 mutations in myeloid malignancies: A brief report of 10 patients
Fms-like tyrosine kinase (FLT3) plays an essential role in hematopoiesis [1]. Its somatic mutations occur in approximately one-third of patients with acute myeloid leukemia (AML), and have important prognostic and therapeutic implications in myeloid malignancies, especially in AML [2 –4]. Two common subtypes of FLT3 mutations have been well described: internal tandem duplication (ITD) in the juxtamembrane and a recurrent amino acid substitution or deletion in the activation loop of the tyrosine kinase (TKD). (Source: Leukemia Research)
Source: Leukemia Research - July 21, 2018 Category: Hematology Authors: Alexandra Higgins, Abhishek Mangaonkar, Mehrdad Hefazi Torghabeh, David Viswanatha, Pedro Horna, James Foran, Naseema Gangat Tags: Letter to the Editor Source Type: research
