Search

Your search keyword '"Jitkova Y"' showing total 2 results
Start Over Author "Jitkova Y" Journal signal transduction and targeted therapy
2 results on '"Jitkova Y"'

1. Correction: Activation of RAS/MAPK pathway confers MCL-1 mediated acquired resistance to BCL-2 inhibitor venetoclax in acute myeloid leukemia.

Author

Zhang Q, Riley-Gillis B, Han L, Jia Y, Lodi A, Zhang H, Ganesan S, Pan R, Konoplev SN, Sweeney SR, Ryan JA, Jitkova Y, Dunner K Jr, Grosskurth SE, Vijay P, Ghosh S, Lu C, Ma W, Kurtz S, Ruvolo VR, Ma H, Weng CC, Ramage CL, Baran N, Shi C, Cai T, Davis RE, Battula VL, Mi Y, Wang J, DiNardo CD, Andreeff M, Tyner JW, Schimmer A, Letai A, Padua RA, Bueso-Ramos CE, Tiziani S, Leverson J, Popovic R, and Konopleva M

Published
2022
Full Text
View/download PDF

2. Activation of RAS/MAPK pathway confers MCL-1 mediated acquired resistance to BCL-2 inhibitor venetoclax in acute myeloid leukemia.

Author

Zhang Q, Riley-Gillis B, Han L, Jia Y, Lodi A, Zhang H, Ganesan S, Pan R, Konoplev SN, Sweeney SR, Ryan JA, Jitkova Y, Dunner K Jr, Grosskurth SE, Vijay P, Ghosh S, Lu C, Ma W, Kurtz S, Ruvolo VR, Ma H, Weng CC, Ramage CL, Baran N, Shi C, Cai T, Davis RE, Battula VL, Mi Y, Wang J, DiNardo CD, Andreeff M, Tyner JW, Schimmer A, Letai A, Padua RA, Bueso-Ramos CE, Tiziani S, Leverson J, Popovic R, and Konopleva M

Subjects
Cell Line, Tumor, Drug Resistance, Neoplasm, Humans, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute metabolism, MAP Kinase Signaling System drug effects, Myeloid Cell Leukemia Sequence 1 Protein genetics, Myeloid Cell Leukemia Sequence 1 Protein metabolism, Proto-Oncogene Proteins c-bcl-2 antagonists & inhibitors, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 metabolism, Sulfonamides pharmacology, ras Proteins
Abstract

Despite high initial response rates, acute myeloid leukemia (AML) treated with the BCL-2-selective inhibitor venetoclax (VEN) alone or in combinations commonly acquires resistance. We performed gene/protein expression, metabolomic and methylation analyses of isogenic AML cell lines sensitive or resistant to VEN, and identified the activation of RAS/MAPK pathway, leading to increased stability and higher levels of MCL-1 protein, as a major acquired mechanism of VEN resistance. MCL-1 sustained survival and maintained mitochondrial respiration in VEN-RE cells, which had impaired electron transport chain (ETC) complex II activity, and MCL-1 silencing or pharmacologic inhibition restored VEN sensitivity. In support of the importance of RAS/MAPK activation, we found by single-cell DNA sequencing rapid clonal selection of RAS-mutated clones in AML patients treated with VEN-containing regimens. In summary, these findings establish RAS/MAPK/MCL-1 and mitochondrial fitness as key survival mechanisms of VEN-RE AML and provide the rationale for combinatorial strategies effectively targeting these pathways., (© 2022. The Author(s).)

Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results