Dataset Information

In-Depth Proteomics Reveals Selective EV Protein Sorting and Pathway Perturbation in AML upon Synergistic FLT3 and Hedgehog Pathway Inhibition

ABSTRACT: Acute myeloid leukemia (AML) is an aggressive cancer mainly affecting bone marrow and blood with a high relapse incidence and mortality rate. Approximately one third of AML patients carry an fms-like tyrosine kinase 3 (FLT3) mutation, which is often associated with GLI expression and Hedgehog signaling, leading to tumor proliferation. AML cells shape their microenvironment into a leukemia-permissive space by releasing extracellular vesicles (EVs). EVs can transfer chemoresistance and thereby play an important role in refractory and relapsing diseases. Here, we discovered a synergistic effect of a combined treatment with the FLT3 inhibitor Crenolanib and the Hedgehog pathway inhibitor HPI-1 in the AML cell lines MOLM-14 and MV4-11. In-depth comparative proteomics revealed alterations in the cellular and the EV proteome upon single or combined inhibition of FLT3 and GLI, highlighting affected pathways. By comparing the cellular and EV proteomes, we report that transport of ribosomal proteins such as RPS26 and RPL27A and ErbB pathway members such as GAB1, GRB2 and SHC1 to EVs is selectively avoided upon treatment with Crenolanib. Ribosomal and ErbB signaling pathway proteins may play an important role in microenvironmental modulation by EVs, and Crenolanib treatment potentially acts by interfering with leukemia niche formation.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Acute Leukemia

SUBMITTER: Gabriele Blümel

LAB HEAD: Christof Regl

PROVIDER: PXD061404 | Pride | 2025-09-29

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20210618_CoB_uPAC_700min_TMTpro_Ctrl_plex_1ug_1-9_1.2m_z_01_87.raw	Raw
	20210618_CoB_uPAC_700min_TMTpro_EV_plex_2ug_1-12_01.raw	Raw
	20210618_CoB_uPAC_700min_TMTpro_EV_plex_CF1_2.4ug_1-12_01.raw	Raw
	20210618_CoB_uPAC_700min_TMTpro_EV_plex_CF2_2.4ug_1-12_01.raw	Raw
	20210618_CoB_uPAC_700min_TMTpro_EV_plex_CF3_2.4ug_1-12_01.raw	Raw

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Publications

Selective EV Protein Sorting and Pathway Perturbation in AML Upon Synergistic FLT3 and Hedgehog Pathway Inhibition.

Blöchl Constantin C Blümel Gabriele G Wolf Martin M Regl Christof C Binder Heide-Marie HM Tesanovic Suzana S Lankes Daniel D Maeding Nicole N Krenn Peter W PW Strunk Dirk D Aberger Fritz F Huber Christian G CG

Journal of extracellular vesicles 20250901 9

Acute myeloid leukaemia (AML) is a haematologic malignancy with high relapse incidence and mortality. Approximately one-third of AML patients carry an fms-like tyrosine kinase 3 (FLT3) mutation, often associated with GLI expression and Hedgehog signalling. AML cells shape their microenvironment into a leukaemia-permissive space by releasing extracellular vesicles (EVs). EVs can transfer chemoresistance and thereby play an important role in refractory and relapsing diseases. Here, we discovered a ...[more]

PMID: 40985884

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