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Characterization of acute myeloid leukemia with del(9q) - Impact of the genes in the minimally deleted region.

Abstract：

:Acute myeloid leukemia is an aggressive disease that arises from clonal expansion of malignant hematopoietic precursor cells of the bone marrow. Deletions on the long arm of chromosome 9 (del(9q)) are observed in 2% of acute myeloid leukemia patients. Our deletion analysis in a cohort of 31 del(9q) acute myeloid leukemia patients further supports the importance of a minimally deleted region composed of seven genes potentially involved in leukemogenesis: GKAP1, KIF27, C9ORF64, HNRNPK, RMI1, SLC28A3 and NTRK2. Importantly, among them HNRNPK, encoding heterogeneous nuclear ribonucleoprotein K is proposed to function in leukemogenesis. We show that expression of HNRNPK and the other genes of the minimally deleted region is significantly reduced in patients with del(9q) compared with normal karyotype acute myeloid leukemia. Also, two mRNAs interacting with heterogeneous nuclear ribonucleoprotein K, namely CDKN1A and CEBPA are significantly downregulated. While the deletion size is not correlated with outcome, associated genetic aberrations are important. Patients with an additional t(8;21) show a good prognosis. RUNX1-RUNX1T1, which emerges from the t(8;21) leads to transcriptional down-regulation of CEBPA. Acute myeloid leukemia patients with mutations in CEBPA have a good prognosis as well. Interestingly, in del(9q) patients with CEBPA mutation mRNA levels of HNRNPK and the other genes located in the minimally deleted region is restored to normal karyotype level. Our data indicate that a link between CEBPA and the genes of the minimally deleted region, among them HNRNPK contributes to leukemogenesis in acute myeloid leukemia with del(9q).

journal_name

Leuk Res

journal_title

Leukemia research

authors

Naarmann-de Vries IS,Sackmann Y,Klein F,Ostareck-Lederer A,Ostareck DH,Jost E,Ehninger G,Brümmendorf TH,Marx G,Röllig C,Thiede C,Crysandt M

doi

10.1016/j.leukres.2018.11.007

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

15-23

eissn

0145-2126

issn

1873-5835

pii

S0145-2126(18)30468-5

journal_volume

76

pub_type

杂志文章

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