Log in to search using one of your social media accounts:

 

GATA2 haploinsufficiency accelerates EVI1-driven leukemogenesis

Chromosomal rearrangements between 3q21 and 3q26 induce inappropriate EVI1 expression by recruiting a GATA2-distal hematopoietic enhancer (G2DHE) to the proximity of the EVI1 gene, leading to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The acquisition of G2DHE by the EVI1 gene reciprocally deprives this enhancer of 1 of the 2 GATA2 alleles, resulting in a loss-of-function genetic reduction in GATA2 abundance. Because GATA2 haploinsufficiency is strongly associated with MDS and AML, we asked whether EVI1 misexpression and GATA2 haploinsufficiency both contributed to the observed leukemogenesis by using a 3q21q26 mouse model that recapitulates the G2DHE-driven EVI1 misexpression, but in this case, it was coupled to a Gata2 heterozygous germ line deletion. Of note, the Gata2 heterozygous deletion promoted the EVI1-provoked leukemic transformation, resulting in early onset of leukemia. The 3q21q26 mice suffered from leukemia in which B220+ cells and/or Gr1+ leukemic cells occupied their bone marrows. We found that the B220+Gr1–c-Kit+ population contained leukemia-initiating cells and supplied Gr1+ leukemia cells in the 3q21q26 leukemia. When Gata2 expression levels in the B220+Gr1–c-Kit+ cells were decreased as a result of Gata2 heterozygous deletion or spontaneous phenomenon, myeloid differentiation of the B220+Gr1–c-Kit+ cells was suppressed, and the cells acquired induced proliferation as well as B-lymphoid–primed characteristics. C...
Source: Blood - Category: Hematology Authors: Tags: Myeloid Neoplasia Source Type: research

Related Links:

Allogeneic stem cell transplant (ASCT) with HLA matched donors is increasingly used for older patients with AML/MDS. It remains unclear if haploidentical transplantation (haploSCT) is a suitable option for older patients with this disease. We analyzed 43 patients with AML/MDS (median age 61 years) who underwent a haploSCT at our institution. All the patients received a fludarabine-melphalan-based reduced-intensity conditioning regimen and post-transplant cyclophosphamide-based GVHD prophylaxis. Except one patient who had early death, the remaining 42 patients (98%) engrafted donor cells.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Bone Marrow Transplantation, Published online: 11 September 2017; doi:10.1038/bmt.2017.171
Source: Bone Marrow Transplantation - Category: Hematology Authors: Source Type: research
Validation of the revised IPSS at transplant in patients with myelodysplastic syndrome/transformed acute myelogenous leukemia receiving allogeneic stem cell transplantation: a retrospective analysis of the EBMT chronic malignancies working party Bone Marrow Transplantation advance online publication, September 11 2017. doi:10.1038/bmt.2017.171 Authors: C Scheid, L de Wreede, A van Biezen, C Koenecke, G Göhring, L Volin, J Maertens, J Finke, J Passweg, D Beelen, J J Cornelissen, M Itälä-Remes, P Chevallier, N Russell, E Petersen, N Milpied, C Richard Espiga, A Peniket, J Sierra, G Mufti, C Crawley, J H Ve...
Source: Bone Marrow Transplantation - Category: Hematology Authors: Source Type: research
Rationale: Myeloid sarcoma (MS) and leukemia cutis (LC) are extramedullary tumors comprising myeloid blasts. They can occur de novo or concurrently with hematological disorders, usually acute myeloid leukemia (AML). AML chemotherapy is generally the initial therapy for MS and LC, and hematopoietic stem cell transplantation (HSCT) can be considered as additional therapy. However, treatment for older patients who are unable to continue intensive chemotherapy is not currently standardized. Patient concerns: A 71-year-old Japanese woman was diagnosed with multiple MSs associated with myelodysplastic syndrome (MDS), using bone...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
Allogeneic hematopoietic stem cell transplantation (AHSCT) is a successful treatment modality for AML and MDS. Information on transplant outcomes among older patients is limited because of concern of adverse transplant-related mortality (TRM) and poor overall survival (OS).
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Post-transplant relapse remains a major cause of treatment failure in patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Understanding of the biology of relapse and response to azacitidine treatment remains limited.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥70 years with hematologic malignancies across the United States. Adults ≥70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥70 years unde...
Source: Blood - Category: Hematology Authors: Tags: Transplantation Source Type: research
Hematopoietic stem cell transplantation (HSCT) is considered the gold standard for treatment of hematologic malignancies, including Fanconi anemia (FA), a cancer-prone disease with extremely high incidence of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, eradication of residual leukemia stem cells (LSCs), which often contributes to relapse, remains the challenge for HSCT. Here we investigate the interaction between leukemic mesenchymal niche and donor hematopoietic stem progenitor cells (HSPCs) by modeling FA HSCT.
Source: Experimental Hematology - Category: Hematology Authors: Source Type: research
The number of allogeneic hematopoietic stem cell transplantations (allo-HCTs) performed each year with curative intent for older adults with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) has continued to rise over the past decade. Much of the progress in the use of allo-HCT in older adults is due to the use of reduced-intensity conditioning (RIC) regimens, which have allowed many older patients with AML or MDS to receive curative allo-HCT [1]. Without RIC, these older patients would otherwise be unfit for allo-HCT because of the toxicity associated with myeloablative conditioning regimens.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
The number of allogeneic transplants performed each year with curative intent for older adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) continued to rise during the past decade. Much of the progress in the use of alloHCT in older adults is due to reduced-intensity conditioning (RIC) regimens, which have allowed many older patients with AML or MDS to receive curative allogeneic hematopoietic cell transplantation (alloHCT).1 Without RIC, these older patients would otherwise be unfit for alloHCT because of the toxicities of myeloablative conditioning.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
More News: Acute Leukemia | Acute Myeloid Leukemia | Genetics | Leukemia | Mergers and Aquisitions | Myelodysplastic Syndrome | Transplants