Stayin ‘ alive: BCL-2 proteins in the hematopoietic system
The hematopoietic system consists of numerous cellular components fulfilling highly specialized tasks in the organism. Due to their restricted life-span a constant blood cell generation is required for homeostasis. Hematopoietic stem cells (HSCs) guarantee this steady supply giving rise to multipotent progenitors that differentiate into all mature blood cell lineages in a process called hematopoiesis. Programmed cell death plays an important role in this meticulously balanced process by eliminating excess or damaged cells and terminating hematopoiesis after increased blood formation. (Source: Experimental Hematology)
Source: Experimental Hematology - March 18, 2022 Category: Hematology Authors: Patricia MA Zehnle, Ying Wu, Henrike Pommerening, Miriam Erlacher Source Type: research
CRLF2 overexpression results in reduced B-cell differentiation and upregulated E2F signaling in the Dp16 mouse model of Down syndrome
Children with Down syndrome (DS) are 10-fold more likely to develop B-cell acute lymphoblastic leukemia (B-ALL), with a higher frequency of rearrangements resulting in overexpression of cytokine receptor-like factor 2 (CRLF2). Here, we investigated the impact of CRLF2 overexpression on B-cell progenitor proliferation, immunophenotype, and gene expression profile in the Dp(16)1Yey (Dp16) mouse model of DS compared with wild-type (WT) mice. CRLF2 overexpression enhanced immature B-lymphoid colony development and increased the proportion of less differentiated pre-pro-B cells, with a greater effect in Dp16 versus WT. (Source:...
Source: Experimental Hematology - March 16, 2022 Category: Hematology Authors: Jacob J. Junco, Barry Zorman, Vincent U. Gant, Jaime Mu ñoz, H. Daniel Lacorazza, Pavel Sumazin, Karen R. Rabin Tags: Brief Communication Source Type: research
CRLF2 overexpression results in reduced B cell differentiation and upregulated E2F signaling in the Dp16 mouse model of Down syndrome
Children with Down syndrome (DS) have a 10-fold increased risk of developing B cell acute lymphoblastic leukemia (B-ALL), and have poorer outcomes due to both increased relapse and treatment-related mortality [1, 2]. The spectrum of cytogenetic alterations is very different in DS compared to non-DS ALL. Approximately half of DS-ALL cases have cytokine receptor-like factor 2 rearrangements (CRLF2-R), compared to only 5-10% of non-DS ALL cases, with half of these also having Janus Kinase 2 (JAK2)-activating point mutations [3-8]. (Source: Experimental Hematology)
Source: Experimental Hematology - March 16, 2022 Category: Hematology Authors: Jacob J. Junco, Barry Zorman, Vincent U. Gant, Jaime Mu ñoz, H. Daniel Lacorazza, Pavel Sumazin, Karen R. Rabin Source Type: research
Combination strategies to promote sensitivity to cytarabine-induced replication stress in acute myeloid leukemia with and without DNMT3A mutations
Acute myeloid leukemia (AML) is an aggressive malignancy of the blood system and the most common acute leukemia in adults (2,3). Improvements in chemotherapy combined with a limited number of targeted approaches thanks to better understanding of the disease mechanisms significantly extended survival in younger patients. Yet, the outcomes in advanced-age AML patients (65 and older, constituting more than half of all cases) remain dismal. Although studies demonstrated survival benefit of induction chemotherapy dose intensification (4,5), most patients are unable to tolerate aggressive treatment due to comorbidities and frail...
Source: Experimental Hematology - March 16, 2022 Category: Hematology Authors: Daniil E Shabashvili, Yang Feng, Prabhjot Kaur, Kartika Venugopal, Olga A Guryanova Source Type: research
CRISPR –Cas9 gene editing induced complex on-target outcomes in human cells
Clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 has been a promising tool for gene engineering, such as correcting disease-associated mutant alleles in somatic or stem cells [1]. Cas9 is a single endonuclease evolved in bacteria and archaea to function as a natural adaptive immune system [2, 3]. Cas9 programmed with crRNA (CRISPR RNA) and tracrRNA (trans-activating crRNA) (Cas9-sgRNA ribonucleoprotein complex) has HNH and RuvC nuclease domains to cleave target DNA, generating two blunt ends of double-strand breaks (DSBs), usually three bp upstream of a protospacer adjacent motif (PAM, NGG for SpCa...
Source: Experimental Hematology - March 15, 2022 Category: Hematology Authors: Wei Wen, Xiao-Bing Zhang Source Type: research
Postnatal conservation of human blood- and marrow-specific CD34+ hematopoietic phenotypes
Hematopoiesis is a hierarchically organized process enabling the lifelong output of mature blood cells from relatively small numbers of hematopoietic stem cells (HSCs). Nevertheless, there is growing evidence of heterogeneity in how this process is determined and executed throughout life [1 –3]. In humans, HSCs are defined functionally by their retrospectively demonstrated display of a very extensive self-sustaining ability, as revealed using either long-term clonal tracking or serial transplant evidence of sustained peripheral blood (PB) cell output [4–8]. (Source: Experimental Hematology)
Source: Experimental Hematology - March 11, 2022 Category: Hematology Authors: Colin A. Hammond, Connie J. Eaves Tags: Article Source Type: research
Epigenetic Maintenance Strategies after Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a 5-year survival rate of 29.5% (1). In recent years, an increased understanding of AML molecular abnormalities has led to the development of targeted therapies for some of the characterized mutations, providing patients with more treatment options (2). Many mutations however still lack defined interventions. The interest in immunotherapeutic mechanisms therefore remains high, particularly in the context of hematopoietic stem cell transplantation (HSCT). (Source: Experimental Hematology)
Source: Experimental Hematology - March 11, 2022 Category: Hematology Authors: Yu Yan, Ram Upadhyaya, Vivian Weixuan Zhang, Tobias Berg Tags: Review Source Type: research
Post-natal conservation of human blood and marrow-specific CD34+ hematopoietic phenotypes
Introduction (Source: Experimental Hematology)
Source: Experimental Hematology - March 11, 2022 Category: Hematology Authors: Colin A. Hammond, Connie J. Eaves Tags: Article Source Type: research
Ruxolitinib ameliorates progressive anemia and improves survival during episodes of emergency granulopoiesis in Fanconi C −/− mice.
Fanconi anemia (FA) is an inherited disorder caused by mutation of one of the 21+ Fanconi DNA-repair genes (1). The FA phenotype may include skeletal anomalies and various carcinomas (2,3). Hematopoietic abnormalities include anemia with progression to BMF in childhood, or clonal progression to AML in adolescence (4). Allogenic stem cell transplantation is the main approach to severe FA hematologic manifestations (5). (Source: Experimental Hematology)
Source: Experimental Hematology - March 9, 2022 Category: Hematology Authors: Shirin Hasan, Liping Hu, Olatundun Williams, Elizabeth A. Eklund Source Type: research
Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - March 1, 2022 Category: Hematology Source Type: research
Heterozygous Dnmt3a R878C Induces Expansion of Quiescent Hematopoietic Stem Cell Pool
Acute myeloid leukemia (AML) is a genetically heterogeneous disease characterized by clonal proliferation of myeloid progenitors and differentiation block. Clonal cytogenetic abnormalities are one of the most important prognostic factors in AML and are used to guide risk-adapted treatment strategies for patients. However, approximately 40% –50% of de novo adult AML patients have a normal karyotype and therefore lack informative cytogenetic markers (1). Recently, in cytogenetically-normal AML (CN-AML), acquired somatic mutations that can provide prognostic information were identified by comprehensive mutational analysis (...
Source: Experimental Hematology - March 1, 2022 Category: Hematology Authors: Takashi Higo, Yutaro Suzuki, Michiaki Sato, Junji Koya, Hideaki Mizuno, Masashi Miyauchi, Yosuke Masamoto, Keisuke Kataoka, Yoshiki Sumitomo, Takako Tsuruta-Kishino, Tomohiko Sato, Mineo Kurokawa Tags: Article Source Type: research
A high prevalence of myeloid malignancies in progeria with Werner syndrome is associated with p53 insufficiency
Werner syndrome (WS) is a progeroid syndrome characterized by the early onset of aging-related symptoms [1,2]. It is caused by mutations in the WRN gene on 8p12, which encodes the RecQ type DNA helicase. The WRN helicase belongs to a DEAH box-containing RecQ family of helicases and has a high degree of helicase activity for the unwinding of unusual DNA structures, such as G4 quadruplex sequences and four-way junctions that resemble intermediates of DNA repair and telomere maintenance. It has been hypothesized that WRN plays a role in the resolution of potentially damaging, complex DNA structures that were accidentally form...
Source: Experimental Hematology - February 28, 2022 Category: Hematology Authors: Hisaya Kato, Yoshiro Maezawa, Dai Nishijima, Eisuke Iwamoto, June Takeda, Takashi Kanamori, Masaya Yamaga, Tatsuzo Mishina, Yusuke Takeda, Shintaro Izumi, Yutaro Hino, Hiroyuki Nishi, Jun Ishiko, Masahiro Takeuchi, Hiyori Kaneko, Masaya Koshizaka, Naoya M Tags: Brief Communication Source Type: research
High prevalence of myeloid malignancies in progeria with Werner syndrome is associated with p53 insufficiency
Werner syndrome (WS) is a progeroid syndrome caused by mutations in the WRN gene, which encodes the RecQ type DNA helicase for the unwinding of unusual DNA structures and is implicated in DNA replication, DNA repair, and telomere maintenance. WS patients are prone to develop malignant neoplasms, including hematological malignancies. However, the pathogenesis of WS-associated hematological malignancies remains uncharacterized. Here we investigated the somatic gene mutations in WS-associated MDS/AML. (Source: Experimental Hematology)
Source: Experimental Hematology - February 28, 2022 Category: Hematology Authors: Hisaya Kato, Yoshiro Maezawa, Dai Nishijima, Eisuke Iwamoto, June Takeda, Takashi Kanamori, Masaya Yamaga, Tatsuzo Mishina, Yusuke Takeda, Shintaro Izumi, Yutaro Hino, Hiroyuki Nishi, Jun Ishiko, Masahiro Takeuchi, Hiyori Kaneko, Masaya Koshizaka, Naoya M Tags: Brief Communications Source Type: research
α4-Integrin deficiency in human CD34+ cells engenders precocious erythroid differentiation but inhibits enucleation
The functional impact of integrin expression in erythropoiesis has been previously emphasized through its decisive influence on erythroid cell –microenvironment (matrix and cellular) interactions, especially under conditions of stress. Beyond that, in several in vitro studies the relationship between the two erythroid integrins, α4 and α5, has been incongruous in terms of a proliferative support, either synergistic or antagonistic, whe reas a dominant influence of α4 integrin on terminal erythropoiesis in vitro and in vivo has been consistently emphasized. (Source: Experimental Hematology)
Source: Experimental Hematology - February 26, 2022 Category: Hematology Authors: Tatyana Ulyanova, Jennifer M. Cherone, Pavel Sova, Thalia Papayannopoulou Tags: Regular submission Source Type: research
Radiation-free reduced-intensity hematopoietic stem cell transplantation with in vivo T-cell depletion from matched related and unrelated donors for Fanconi anemia: prognostic factor analysis
Fanconi anemia (FA) is a genetically and phenotypically heterogeneous autosomal or X ‐linked recessive disorder, clinically characterized by congenital anomalies and progressive bone marrow failure (BMF), which is the main life-threatening problem in these patients [1] Hypersensitivity to pro-inflammatory cytokines and intolerance to oxidative stress lead to apoptotic contraction of the stem cell pool and subsequently BMF in FA patients [2]. Predisposition to developing clonal cytogenetic abnormalities, myelodysplasia, acute myeloid leukemia (AML), and solid tumors (especially squamous cell carcinoma) because of inhibiti...
Source: Experimental Hematology - February 20, 2022 Category: Hematology Authors: Tahereh Rostami, Seyed Ali Mousavi, Amir Kasaeian, Azadeh Kiumarsi, Soroush Rad, Marjan Yaghmaie, Ardeshir Ghavamzadeh, Seied Asadollah Mousavi Tags: Article Source Type: research
