Open AccessCombined loss of function of two different loci of miR-15/16 drives the pathogenesis of acute myeloid leukemia
Author(s) -
Francesca Lovat,
Giovanni Nigita,
Rosario Distefano,
Tatsuya Nakamura,
Pierluigi Gasparini,
Luisa Tomasello,
Paolo Fadda,
Narmin Ibrahimova,
Silvia Catricalà,
Alexey Palamarchuk,
Michael A. Caligiuri,
Anna Gallì,
Luca Malcovati,
Mark D. Minden,
Carlo M. Croce
Publication year - 2020
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2003597117
Subject(s) - myeloid leukemia , pathogenesis , function (biology) , leukemia , myeloid , cancer research , medicine , biology , computational biology , genetics , immunology
Significance The loss of miR-15a/16-1 on chromosome 13q14 and miR-15b/16-2 on chromosome 3q25 is critical for the development of AML in mice. We hypothesized that, at least, a fraction of human AML patients could undergo a comparable mechanism. Here, we evaluated the expression of the two miR-15/16 clusters in 93 MDS patients and 139 AML patients. A significant reduction of miR-15a, miR-15b, and miR-16 expression can predict the progression from MDS to AML transformation. We demonstrated in 40% of AML cell lines analyzed, a combined reduction of miR-15a/-15b expression and an overexpression of their direct/indirect targets. MiR-15/16 cluster expression can be a valuable marker to stratify AML patients for a combined therapy, based on venetoclax and anti-ROR1 antibody.
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