STK3 is a therapeutic target for a subset of acute myeloid leukemias

TY - JOUR

T1 - STK3 is a therapeutic target for a subset of acute myeloid leukemias

AU - Camgoz, Aylin

AU - Paszkowski-Rogacz, Maciej

AU - Satpathy, Shankha

AU - Wermke, Martin

AU - Hamann, Martin V.

AU - von Bonin, Malte

AU - Choudhary, Chunaram

AU - Knapp, Stefan

AU - Buchholz, Frank

PY - 2018/5/22

Y1 - 2018/5/22

N2 - Acute myeloid leukemia (AML) is characterized by uncontrolled proliferation and accumulation of immature myeloblasts, which impair normal hematopoiesis. While this definition categorizes the disease into a distinctive group, the large number of different genetic and epigenetic alterations actually suggests that AML is not a single disease, but a plethora of malignancies. Still, most AML patients are not treated with targeted medication but rather by uniform approaches such as chemotherapy. The identification of novel treatment options likely requires the identification of cancer cell vulnerabilities that take into account the different genetic and epigenetic make-up of the individual tumors. Here we show that STK3 depletion by knock-down, knock-out or chemical inhibition results in apoptotic cells death in some but not all AML cell lines and primary cells tested. This effect is mediated by a premature activation of cyclin dependent kinase 1 (CDK1) in presence of elevated cyclin B1 levels. The anti-leukemic effects seen in both bulk and progenitor AML cells suggests that STK3 might be a promising target in a subset of AML patients.

AB - Acute myeloid leukemia (AML) is characterized by uncontrolled proliferation and accumulation of immature myeloblasts, which impair normal hematopoiesis. While this definition categorizes the disease into a distinctive group, the large number of different genetic and epigenetic alterations actually suggests that AML is not a single disease, but a plethora of malignancies. Still, most AML patients are not treated with targeted medication but rather by uniform approaches such as chemotherapy. The identification of novel treatment options likely requires the identification of cancer cell vulnerabilities that take into account the different genetic and epigenetic make-up of the individual tumors. Here we show that STK3 depletion by knock-down, knock-out or chemical inhibition results in apoptotic cells death in some but not all AML cell lines and primary cells tested. This effect is mediated by a premature activation of cyclin dependent kinase 1 (CDK1) in presence of elevated cyclin B1 levels. The anti-leukemic effects seen in both bulk and progenitor AML cells suggests that STK3 might be a promising target in a subset of AML patients.

U2 - 10.18632/oncotarget.25238

DO - 10.18632/oncotarget.25238

M3 - Journal article

C2 - 29876001

SN - 1949-2553

VL - 9

SP - 25458

EP - 25473

JO - OncoTarget

JF - OncoTarget

IS - 39

ER -