CD45dimCD34+CD38 −CD133+ cells have the potential as leukemic stem cells in acute myeloid leukemia

Leukemia stem cells (LSCs) in play an important role in the initiation, relapse, and progression of acute myeloid leukemia (AML), and in the development of chemotherapeutic drug resistance in AML. Studies rega...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Research article Source Type: research

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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
Fifty ‐two patients with relapsed/refractory acute myeloid leukemia (AML) were treated with clofarabine, cytarabine, and mitoxantrone. The overall response rate (ORR) was 90.4% (complete remission, CR: 69.2%; CR with incomplete hematological recovery, CRi: 21.2%), with 22 CR/CRi patients undergoing allo geneic hematopoietic stem cell transplantation (allo‐HSCT), while in CR; resulting in a 2‐year OS of 84.3% in CR patients and 90% in patients receiving allo‐HSCT. Clofarabine, cytarabine, and mitoxantrone resulted in high ORR and was safe in refractory/relapsed AML. AbstractClofarabine is active in refractory/relaps...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Abstract N6-methyladenosine (m6A), the most abundant internal modification in mRNA, has been implicated in tumorigenesis. As an m6A demethylase, ALKBH5 has been shown to promote the development of breast cancer and brain tumors. However, in acute myeloid leukemia (AML), ALKBH5 was reported to be frequently deleted, implying a tumor-suppressor role. Here, we show that ALKBH5 deletion is rare in human AML; instead, ALKBH5 is aberrantly overexpressed in AML. Moreover, its increased expression correlates with poor prognosis in AML patients. We demonstrate that ALKBH5 is required for the development and maintenance of ...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
sse Emilie Bérard Christian Récher The prognostic impact of immunophenotypic CD34+CD38-CD123+ leukemic stem cell (iLSC) frequency at diagnosis has been demonstrated in younger patients treated by intensive chemotherapy, however, this is less clear in older patients. Furthermore, the impact of iLSC in patients treated by hypomethylating agents is unknown. In this single-center study, we prospectively assessed the CD34+CD38-CD123+ iLSC frequency at diagnosis in acute myeloid leukemia (AML) patients aged 60 years or older. In a cohort of 444 patients, the median percentage of iLSC at diagnosis was 4.3%. ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract Over the past decade, our increased understanding of the interactions between the immune system and cancer cells has led to paradigm shifts in the clinical management of solid and hematologic malignancies. The incorporation of immune-targeted strategies into the treatment landscape of acute myeloid leukemia (AML), however, has been challenging. While this is in part due to the inability of the immune system to mount an effective tumor-specific immunogenic response against the heterogeneous nature of AML, the decreased immunogenicity of AML cells also represents a major obstacle in the effort to design eff...
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research
Abstract Hematopoiesis is a tightly regulated process that originates from highly specialized cells, hematopoietic stem cells (HSCs). Many cancers can arise and be maintained by malignant stem cells. In acute myeloid leukemia, leukemic stem cells (LSCs) are identified by their immunophenotype, which is partly shared with normal HSCs (CD34+CD38-). However, LSCs also possess unique immunophenotypic features that can be used to distinguish them from HSCs and therapeutically target them. One such unique immunophenotypic marker is CD123, found to be aberrantly expressed in leukemic stem, progenitor, and blast cells. Th...
Source: The Medical Clinics of North America - Category: General Medicine Authors: Tags: Hematol Oncol Clin North Am Source Type: research
Conclusion: It is also concluded that GFI1 overexpression in patients with high MPO levels, such as those of the APL subtype, is correlated with favorable disease prognosis as supported by other studies which demonstrate that increased peroxide activity and GFI1 are independently correlated with a favorable prognosis
Source: Journal of Cancer Research and Therapeutics - Category: Cancer & Oncology Authors: Source Type: research
Abstract Despite recent therapeutic advancements, acute myeloid leukemia (AML) remains a challenging clinical entity with overall poor outcomes. Given the demonstrable role of T cellmediated immunity in response to allogeneic stem cell transplantation and donor lymphocyte infusions, strategies that enhance immune activation and mitigate immune dysfunction represent attractive therapeutic platforms to improve clinical outcomes in AML. Pre-clinical data suggest that immune dysfunction is a major contributor to AML progression and relapse. Increased expression of immune checkpoints such as programmed death 1 (PD-1) c...
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research
The histone methyltransferase G9a has recently been identified as a potential target for epigenetic therapy of acute myeloid leukemia (AML). However, the effect of G9a inhibition on leukemia stem cells (LSCs),...
Source: Journal of Experimental and Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Research Source Type: research
Abstract TET family members (TETs) encode proteins that represent crucial factors in the active DNA demethylation pathway. Evidence has proved that TET2 mutation is associated with leukemogenesis, drug response, and prognosis in acute myeloid leukemia (AML). However, few studies revealed the TETs expression and its clinical significance in AML. We conducted a detailed expression and prognosis analysis of TETs expression in human AML cell lines and patients by using public databases. We observed that TETs expression especially TET2 and TET3 was closely associated with AML among various human cancers. TET1 expressio...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
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