The U2AF homology motif kinase 1 (UHMK1) is upregulated upon hematopoietic cell differentiation

Author(s)

Barbutti, Isabella ^[1] ; Machado-Neto, Joao Agostinho ^[2] ; Arfelli, Vanessa Cristina ^[3] ; Campos, Paula de Melo ^[1] ; Traina, Fabiola ^[2] ; Olalla Saad, Sara Teresinha ^[1] ; Archangelo, Leticia Frohlich ^{[1, 3]}

Affiliation

^[1] State Univ Campinas UNICAMP, Hematol & Transfus Med Ctr, Carlos Chagas 480, BR-13083878 Campinas, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cellular & Mol Biol & Pathogen Bioagents, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE; v. 1864, n. 3, p. 959-966, MAR 2018.
• Web of Science Citations: 1

Abstract

UHMK1 (KIS) is a nuclear serine/threonine kinase that possesses a U2AF homology motif and phosphorylates and regulates the activity of the splicing factors SF1 and SF3b155. Mutations in these components of the spliceosome machinery have been recently implicated in leukemogenesis. The fact that UHMK1 regulates these factors suggests that UHMK1 might be involved in RNA processing and perhaps leukemogenesis. Here we analyzed UHMK1 expression in normal hematopoietic and leukemic cells as well as its function in leukemia cell line. In the normal hematopoietic compartment, markedly higher levels of transcripts were observed in differentiated lymphocytes (CD4(+), CD8(+) and CD19(+)) compared to the progenitor enriched subpopulation (CD34(+)) or leukemia cell lines. UHMK1 expression was upregulated in megakaryocytic-, monocytic- and granulocytic induced differentiation of established leukemia cell lines and in erythrocytic-induced differentiation of CD34(+) cells. No aberrant expression was observed in patient samples of myelodysplastic syndrome (MDS), acute myeloid (AML) or lymphoblastic (ALL) leukemia. Nonetheless, in MDS patients, increased levels of UHMK1 expression positively impacted event free and overall survival. Lentivirus mediated UHMK1 knockdown did not affect proliferation, cell cycle progression, apoptosis or migration of U937 leukemia cells, although UHMK1 silencing strikingly increased clonogenicity of these cells. Thus, our results suggest that UHMK1 plays a role in hematopoietic cell differentiation and suppression of autonomous clonal growth of leukemia cells. (AU)

• FAPESP's process: 11/51959-0 - Biology of neoplastic diseases of bone marrow
• Grantee: Sara Teresinha Olalla Saad
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/01458-3 - Defining the functional role of the splicing factor regulator (KIS) during leukemogenesis using a murine bone marrow transplantion model
• Grantee: Leticia Fröhlich Archangelo
• Support Opportunities: Research Grants - Young Investigators Grants