Proteomics

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Phosphoproteomics of human MV4-11 AML cells treated with Gilteritinib

ABSTRACT: Internal tandem duplications (ITD) in the receptor tyrosine kinase FLT3 occur in 25% of acute myeloid leukemia (AML) patients and lead to constitutive activation of FLT3, driving leukemia cell survival and proliferation. Quizartinib, crenolanib and gilteritinib are second-generation FLT3 inhibitors (FLT3i) in phase III trials or clinical use for the targeted treatment of FLT3-ITD+ AML. However, they demonstrated only limited benefit and were not curative. A full understanding of cellular resistance factors contributing to this poor response is lacking. Here, we examined cell-autonomous pathways modulated by FLT3i using global translatome and phosphoproteome proteomics to identify non-genetic resistance mechanisms.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Suspension Culture, Leukocyte

DISEASE(S): Acute Leukemia

SUBMITTER: Sebastian Koschade  

LAB HEAD: Christian Münch

PROVIDER: PXD023123 | Pride | 2022-08-25

REPOSITORIES: Pride

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20200620_MV_Phos_F.msf Msf
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20200620_MV_Phos_F2.raw Raw
20200620_MV_Phos_F3.raw Raw
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Publications

The individual components of commercial isometamidium do not possess stronger trypanocidal activity than the mixture, nor bypass isometamidium resistance.

Eze Anthonius A AA   Igoli John J   Gray Alexander I AI   Skellern Graham G GG   De Koning Harry P HP  

International journal for parasitology. Drugs and drug resistance 20190121

The four components present in the trypanocidal treatment Samorin, the commercially available formulation of isometamidium, were separated and purified by column chromatography. These compounds as well as the Samorin mixture and the other phenanthridine trypanocide, homidium, were tested on Trypanosoma congolense and wild type, diamidine- and isometamidium-resistant Trypanosoma brucei brucei strains using an Alamar blue drug sensitivity assay. EC<sub>50</sub> values obtained suggest that M&B4180  ...[more]

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