Antisense STAT3 inhibitor decreases viability of myelodysplastic and leukemic stem cells.
Authors of this article are:
Shastri A, Choudhary G, Teixeira M, Gordon-Mitchell S, Ramachandra N, Bernard L, Bhattacharyya S, Lopez R, Pradhan K, Giricz O, Ravipati G, Wong LF, Cole S, Bhagat TD, Feld J, Dhar Y, Bartenstein M, Thiruthuvanathan VJ, Wickrema A, Ye BH, Frank DA, Pellagatti A, Boultwood J, Zhou T, Kim Y, MacLeod AR, Epling-Burnette PK, Ye M, McCoon P, Woessner R, Steidl U, Will B, Verma A.
A summary of the article is shown below:
Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Transcriptomic analysis of stem and progenitor populations in MDS and AML demonstrated overexpression of STAT3 that was validated in an independent cohort. STAT3 overexpression was predictive of a shorter survival and worse clinical features in a large MDS cohort. High STAT3 expression signature in MDS CD34+ cells was similar to known preleukemic gene signatures. Functionally, STAT3 inhibition by a clinical, antisense oligonucleotide, AZD9150, led to reduced viability and increased apoptosis in leukemic cell lines. AZD9150 was rapidly incorporated by primary MDS/AML stem and progenitor cells and led to increased hematopoietic differentiation. STAT3 knockdown also impaired leukemic growth in vivo and led to decreased expression of MCL1 and other oncogenic genes in malignant cells. These studies demonstrate that STAT3 is an adverse prognostic factor in MDS/AML and provide a preclinical rationale for studies using AZD9150 in these diseases.
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This article is a good source of information and a good way to become familiar with topics such as:
Hematology;Hematopoietic stem cells;Signal transduction;Stem cells
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