Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia
نویسندگان
چکیده
Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells in vivo However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected. Although miR-155 accelerated growth and homing in addition to impairing differentiation, our data underscore the pathophysiological relevance of miR-155 as an accelerator rather than a driver of leukemogenesis. This further highlights the complexity of the oncogenic program of Meis1 to compensate for the loss of a potent oncogene such as miR-155. These findings are highly relevant to current and developing approaches for targeting miR-155 in acute myeloid leukemia.
منابع مشابه
The role of microRNA in acute/chronic, myeloid/lymphocytic leukemia
MicroRNAs are small, non-coding sequences that regulate gene expression by inducing degradation or translational inhibition of target mRNAs. These molecules control many intracellular physiological and pathological processes.Abnormal expression of these moleculs has been described in different cancers including hematopoietic cancers. According to the type of cancer and the stage, miRNA’s expres...
متن کاملPBX3 and MEIS1 Cooperate in Hematopoietic Cells to Drive Acute Myeloid Leukemias Characterized by a Core Transcriptome of the MLL-Rearranged Disease.
Overexpression of HOXA/MEIS1/PBX3 homeobox genes is the hallmark of mixed lineage leukemia (MLL)-rearranged acute myeloid leukemia (AML). HOXA9 and MEIS1 are considered to be the most critical targets of MLL fusions and their coexpression rapidly induces AML. MEIS1 and PBX3 are not individually able to transform cells and were therefore hypothesized to function as cofactors of HOXA9. However, i...
متن کاملHoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia
The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Sy...
متن کاملThe Difference in Initial Leukocyte Count, Bone Marrow Blast Cell Count and CD 34 Expression in Patients with Acute Myeloid Leukemia with and without NPM1 gene Mutation
Background: Mutation in NPM1 gene has been reported to be the most common genetic mutation in de novo acute myeloid leukemia (AML). AML with NPM1 gene mutation usually presents with higher initial leukocyte and blast cell counts and negative CD34 expression. We aimed to investigate the difference of initial leukocyte counts, bone marrow blast cell counts and expression of CD34 among patients wi...
متن کاملTreatment of a Child with Refractory Acute Myeloid Leukemia with Humanized Anti-CD33 Monoclonal Antibody: A Case Report and Review of Drug Development
Background: The induction chemotherapy regimen for acute myeloid leukemia has evolved as once induction is completed patients progress through the consolidation phase and achieve remission in 76% of cases. For patients with relapsed or refractory disease, alternative chemotherapy agents are available. Monoclonal antibody therapy with biological agents, such as the immunotoxin gemtuzumab ozog...
متن کامل