Cancers, Vol. 12, Pages 2427: Isocitrate Dehydrogenase Mutations in Myelodysplastic Syndromes and in Acute Myeloid Leukemias

Cancers, Vol. 12, Pages 2427: Isocitrate Dehydrogenase Mutations in Myelodysplastic Syndromes and in Acute Myeloid Leukemias Cancers doi: 10.3390/cancers12092427 Authors: Ugo Testa Germana Castelli Elvira Pelosi Acute myeloid leukemia (AML) is a heterogeneous disease generated by the acquisition of multiple genetic and epigenetic aberrations which impair the proliferation and differentiation of hematopoietic progenitors and precursors. In the last years, there has been a dramatic improvement in the understanding of the molecular alterations driving cellular signaling and biochemical changes determining the survival advantage, stimulation of proliferation, and impairment of cellular differentiation of leukemic cells. These molecular alterations influence clinical outcomes and provide potential targets for drug development. Among these alterations, an important role is played by two mutant enzymes of the citric acid cycle, isocitrate dehydrogenase (IDH), IDH1 and IDH2, occurring in about 20% of AMLs, which leads to the production of an oncogenic metabolite R-2-hydroxy-glutarate (R-2-HG); this causes a DNA hypermethylation and an inhibition of hematopoietic stem cell differentiation. IDH mutations differentially affect prognosis of AML patients following the location of the mutation and other co-occurring genomic abnormalities. Recently, the development of novel therapies based on the specific targeting of mutant IDH may contribute to new effective treatments of thes...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research

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Abstract The tumor suppressor p53 exerts pivotal roles in hematopoietic stem cell (HSC) homeostasis. Mutations of the TP53 gene have recently been described in individuals with clonal hematopoieis conferring substantial risk of developing blood cancers. In patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), TP53 aberrations - mutations, deletions and a combination thereof - are encountered at a constant frequency of approximately 10%. These aberrations affect HSCs transforming them into preleukemic stem cells, pinpointing their central role in leukemogenesis. AML and MDS with TP53 aberr...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Kobbe Thomas Schroeder To provide long-term outcome data and predictors for response and survival, we retrospectively analyzed all 151 patients with relapse of myeloid neoplasms after allogeneic hematopoietic stem cell transplantation (allo-HSCT) who were uniformly treated with first-line azacitidine (Aza) salvage therapy at our center. Patients were treated for molecular (39%) or hematologic relapse (61%), with a median of 5 cycles of Aza and at least one donor lymphocyte infusion in 70% of patients. Overall response was 46%, with 41% achieving complete (CR) and 5% achieving partial remission. CR was achieved after ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
We compared the transplant outcomes between HID and MSD transplants for AML and MSD aged ≥50 years. The results showed that HID transplant is feasible and safe for elderly AML/MDS patients. AbstractAllogeneic hematopoietic stem cell transplantation (allo ‐HSCT) is a potentially curative therapeutic option for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Increasing data suggest that haploidentical donor (HID) transplantation achieve comparable outcomes with HLA‐matched sibling donor (MSD) in adult AML/MDS. This re trospective study compared the outcomes of AML or MDS patients age ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
our M Abstract Microtransplantation (MT) is based on injection of HLA-mismatched G-CSF mobilized hematopoietic stem cells, in combination with chemotherapy but without use of conditioning regimen nor immunosuppressive drugs. As a result, a transient microchimerism is induced without engraftment. Its efficacy relies both on host immune system stimulation (recipient versus tumor) and on a graft versus tumor effect. Data are scarce and concern mostly Asian patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (HR-MDS). In comparison to conventional treatment without MT, higher complete rem...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
g P Abstract The myelodysplastic syndromes (MDS) share an origin in the hematopoietic stem cell but have otherwise very heterogeneous biological and genetic characteristics. Clinical features are dominated by cytopenia and substantial risk for progression to acute myeloid leukemia. According to the World Health Organisation (WHO) MDS is defined by cytopenia, bone marrow dysplasia, and by certain karyotypic abnormalities. The understanding of disease pathogenesis has undergone major development with the implementation of next generation sequencing, and a closer integration of morphology, cytogenetics and molecular ...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Cells become senescent in response to a variety of circumstances. The vast majority are cases of replicative senescence, somatic cells reaching the Hayflick limit. Cell damage and toxic environments also produce senescence, and senescent cells are also created as a part of the wound healing process. A senescent cell ceases replication and begins to secrete inflammatory and pro-growth signals, altering the nearby extracellular matrix and behavior of surrounding cells - even encouraging them to become senescent as well. Near all senescent cells last a short time only, as they self-destruct or are removed by the immune...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Authors: Gorshein E, Weber UM, Gore S Abstract Introduction: Myelodysplastic Syndrome (MDS) represents a group of cancers characterized by abnormal blood cell formation and maturation, leading to various degrees of cytopenias and potential transformation to acute myeloid leukemia. Deletion of the long arm of chromosome 5 (del(5q)) is the most common clonal chromosomal anomaly in MDS, yet the population in this disease subtype is quite heterogeneous. This manuscript analyzes literature on high-risk MDS with del(5q) abnormalities.Areas covered: The paper will review outcomes with lenalidomide among high-risk MDS pati...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
Relapse after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains a major cause of treatment failure with associated poor prognosis. Low-dose post-HSCT maintenance azacitidine (AZA) has proved to be beneficial in preventing relapses (de Lima et al. Cancer 2010). Herein, we retrospectively evaluated outcomes of patients (pts) treated with low-dose AZA post-HSCT.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 175 Source Type: research
In conclusion, we confirmed that ATPR could induce SKM-1 cells differentiation and its positive influence of DDX23 may provide a new idea to relieve MDS.
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
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