Browsing by Author "Sukhanova, Madina"

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    Assessing copy number abnormalities and copy-neutral loss-of-heterozygosity across the genome as best practice in diagnostic evaluation of acute myeloid leukemia: An evidence-based review from the cancer genomics consortium (CGC) myeloid neoplasms working group
    (Elsevier, 2018) Xu, Xinjie; Bryke, Christine; Sukhanova, Madina; Huxley, Emma; Dash, D. P.; Dixon-Mciver, Amanda; Fang, Min; Griepp, Patricia T.; Hodge, Jennelle C.; Iqbal, Anwar; Jeffries, Sally; Kanagal-Shamanna, Rashmi; Quintero-Rivera, Fabiola; Shetty, Shashi; Slovak, Marilyn L.; Yenamandra, Ashwini; Lennon, Patrick A.; Raca, Gordana; Medical and Molecular Genetics, School of Medicine
    Structural genomic abnormalities, including balanced chromosomal rearrangements, copy number gains and losses and copy-neutral loss-of-heterozygosity (CN-LOH) represent an important category of diagnostic, prognostic and therapeutic markers in acute myeloid leukemia (AML). Genome-wide evaluation for copy number abnormalities (CNAs) is at present performed by karyotype analysis which has low resolution and is unobtainable in a subset of cases. Furthermore, examination for possible CN-LOH in leukemia cells is at present not routinely performed in the clinical setting. Chromosomal microarray (CMA) analysis is a widely available assay for CNAs and CN-LOH in diagnostic laboratories, but there are currently no guidelines how to best incorporate this technology into clinical testing algorithms for neoplastic diseases including AML. The Cancer Genomics Consortium Working Group for Myeloid Neoplasms performed an extensive review of peer-reviewed publications focused on CMA analysis in AML. Here we summarize evidence regarding clinical utility of CMA analysis in AML extracted from published data, and provide recommendations for optimal utilization of CMA testing in the diagnostic workup. In addition, we provide a list of CNAs and CN-LOH regions which have documented clinical significance in diagnosis, prognosis and treatment decisions in AML.
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    PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation
    (American Association for Cancer Research, 2024) Chen, Hongxia; Bai, Yunpeng; Kobayashi, Michihiro; Xiao, Shiyu; Barajas, Sergio; Cai, Wenjie; Chen, Sisi; Miao, Jinmin; Meke, Frederick Nguele; Yao, Chonghua; Yang, Yuxia; Strube, Katherine; Satchivi, Odelia; Sun, Jianmin; Rönnstrand, Lars; Croop, James M.; Boswell, H. Scott; Jia, Yuzhi; Liu, Huiping; Li, Loretta S.; Altman, Jessica K.; Eklund, Elizabeth A.; Sukhanova, Madina; Ji, Peng; Tong, Wei; Band, Hamid; Huang, Danny T.; Platanias, Leonidas C.; Zhang, Zhong-Yin; Liu, Yan; Pediatrics, School of Medicine
    Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells. Implications: Our studies uncover a novel mechanism that fine-tunes oncogenic KIT signaling in leukemia cells and will likely identify PRL2 as a novel therapeutic target in AML with KIT mutations.