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LC-MS3 analysis of Herc1-knockout mouse MLL/AF9 acute myeloid leukemia cells

ABSTRACT: Our CRISPR-based pharmacogenomic screening identified the E3 ubiquitin ligase Herc1 as a key modulator of sensitivity to cytarabine (Ara-C) chemotherapy in the MLL/AF9 (MA) mouse AML model both in vitro and in vivo. To identify the intracellular proteins whose abundance is modulated by Herc1, we performed comparative LC-MS3 analysis of in vitro-cultured MA mouse AML cells that were transduced with either a small-guide RNA targeting Herc1 (i.e., CRISPR-mediated Herc1-knockout) or a control non-targeting small-guide RNA, at steady state or after brief exposure to Ara-C (200 nMol for 6 hours).

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

DISEASE(S): Acute Leukemia

SUBMITTER: François Mercier

LAB HEAD: Francois Mercier

PROVIDER: PXD054402 | Pride | 2024-08-08

REPOSITORIES: Pride

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			Action	DRS
	M-TMT-F1.raw	Raw
	M-TMT-F2.raw	Raw
	M-TMT-F3.raw	Raw
	M-TMT-F4.raw	Raw
	M-TMT-F5.raw	Raw

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Publications

The E3 ubiquitin ligase Herc1 modulates the response to nucleoside analogs in acute myeloid leukemia.

Jankovic Maja M Poon William W L WWL Gonzales-Losada Cristobal C Vazquez Gabriela Galicia GG Sharif-Askari Bahram B Ding Yi Y Craplet-Desombre Constance C Ilie Alexandru A Shi Jiantao J Wang Yongjie Y Jayavelu Ashok Kumar AK Orthwein Alexandre A Mercier François Émile FÉ

Blood advances 20241001 20

<h4>Abstract</h4>For several decades, induction therapy with nucleoside analogs, in particular cytarabine (Ara-C) and, to a lesser extent, fludarabine, has been the standard of care for patients diagnosed with acute myeloid leukemia (AML). However, the antitumor efficacy of nucleoside analogs is often limited by intrinsic and acquired drug resistance, thereby leading to poor therapeutic response and suboptimal clinical outcomes. In this study, we used genome-wide CRISPR-based pharmacogenomic scr ...[more]

PMID: 39093953

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