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MicroRNAs and Chronic Lymphocytic Leukemia

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MicroRNA in Development and in the Progression of Cancer

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Abstract

MicroRNA abnormalities are involved in the development and progression of chronic lymphocytic leukemia (CLL). In the majority of CLL malignant cluster of differentiation CD5+ (B-1) clones, the expression of miR-15a/16 is decreased relative to polyclonal CD5− (B-2) cells. Levels of the anti-apoptotic protein, bcl-2, correlate with the deletion of the Dleu2 region on chromosome 13q14 containing the mir-15a/16-1 loci. The expansion of CD5+ B cells and development of B-1 clones usually precedes CLL disease and is referred to as monoclonal B lymphocytosis (MBL). An early event in MBL may decrease miR-15a/16 expression. In the New Zealand black mouse model of CLL, there is a mutation in the mir-15a/16-1 loci resulting in decreased expression of miR-15a/16 due to a processing defect. Since this is a germline mutation, induced pluripotent stem cells and hematopoietic stem cells were employed to determine the role of decreased miR-15a/16 on B-1 lineage development. Enforced overexpression of miR-15a/16 leads to almost exclusive B-2 development. These results suggest that decreased miR-15a/16 is critical for the development of B-1 cells and the progression to malignant B-1 clonal expansion.

Support: This work was supported by NCI R01CA129826 (ER) and an NSF SIR award (ER)

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Authors and Affiliations

  1. OSEL, CDRH, FDA, White Oak, MD, USA

    Heba Degheidy, Marilyn Lightfoote & Gerald Marti

  2. Pathology and Laboratory Medicine, New Jersey Medical School, MSB C512, 185 S Orange Avenue, 07103, Newark, NJ, USA

    Siddha Kasar, Chingiz Underbayev, Yao Yuan, Smruti Mehta & Prof Elizabeth Raveche Ph.D

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  1. Heba Degheidy
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Correspondence to Elizabeth Raveche Ph.D .

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  1. National Cancer Institute Mouse Cancer Genetics Program, Frederick, Maryland, USA

    Shree Ram Singh

  2. UMDNJ-NJ Medical School, Newark, New Jersey, USA

    Pranela Rameshwar

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Degheidy, H. et al. (2014). MicroRNAs and Chronic Lymphocytic Leukemia. In: Singh, S., Rameshwar, P. (eds) MicroRNA in Development and in the Progression of Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-8065-6_9

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