Dataset Information

Differentially Expressed Proteins in Plasma-Derived Extracellular Vesicles from Chronic Myeloid Leukemia Patients

ABSTRACT: Chronic myeloid leukemia (CML) is driven by the BCR::ABL1 fusion gene. Although tyrosine kinase inhibitors (TKIs) have transformed outcomes, treatment resistance persists. Plasma extracellular vesicles (EVs) reflect their cell of origin and may serve as stable biomarkers. To characterize the plasma EV proteome in CML patients with distinct treatment responses and T315I mutation status. EVs were isolated from the plasma of healthy controls (HC) and CML patients classified as good (GTR) or poor (PTR) treatment responders, treatment-free remission (TFR), and T315I or pre-T315I mutation carriers. EVs were purified by size-exclusion chromatography, characterized by NTA and TEM, and analyzed by label-free mass spectrometry, followed by differential expression, enrichment, and protein–protein interaction analyses. A total of 598 proteins were identified, 257 retained after quality and abundance filtering. Forty-two proteins were differentially expressed among HC, GTR, and PTR groups (p < 0.01), with PTR samples showing marked downregulation of cytoskeletal and chaperone proteins (such as MYH9, HSP90AB1, FERMT3). TFR patients exhibited distinct enrichment in complement and coagulation cascades (C3, C4B, F9, F11) and metabolic pathways. Plasma EV proteomes reflect CML clinical status, revealing immune and cytoskeletal alterations associated with treatment response, remission, and resistance, suggesting potential biomarkers for disease monitoring.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Chronic Myeloid Leukemia

SUBMITTER: Michel Batista

LAB HEAD: Dalila Luciola Zanette

PROVIDER: PXD071200 | Pride | 2026-01-26

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	2020816_138224_Denise_93_23_1.raw	Raw
	2020816_138224_Denise_93_23_2.raw	Raw
	2020816_138324_Denise_143_23_1.raw	Raw
	2020816_138324_Denise_143_23_3.raw	Raw
	2020816_138424_Denise_88_22_1.raw	Raw

Items per page:

1 - 5 of 58

Similar Datasets

Project description:The management of patients with chronic myeloid leukemia (CML) has been revolutionized by the introduction of tyrosine kinase inhibitors (TKIs), which induce deep molecular responses so that treatment can eventually be discontinued, leading to treatment-free remission (TFR) in a subset of patients. Unfortunately, leukemic stem cells (LSCs) often persist and a fraction of these can again expand in about half of patients that attempt TKI discontinuation. In this study, we show that presence of myelofibrosis (MF) at the time of diagnosis is a factor that strongly associates with TFR failure. Fibrotic transformation is governed by the action of several cytokines, and interestingly, some of them have also been described to support LSC persistence. At the cellular level, these could be produced by both malignant cells and by components of the bone marrow (BM) niche, including megakaryocytes (MKs) and mesenchymal stromal cells (MSCs). In our cohort of 57 patients, around 40% presented with MF at diagnosis and the number of blasts in the peripheral blood and BM was significantly elevated in patients with higher grade of MF. Employing a CML transgenic mouse model, we could observe higher levels of alpha-smooth muscle actin (α-SMA) in the BM when compared to control mice. Short-term treatment with the TKI nilotinib, efficiently reduced spleen weight and BCR-ABL1 mRNA levels, while α-SMA expression was only partially reduced. Interestingly, the number of MKs was increased in the spleen of CML mice and elevated in both BM and spleen upon nilotinib treatment. Microarray analysis of human CML- vs healthy donor (HD)-derived MSCs showed an altered expression of gene signatures reflecting fibrosis as well as hematopoietic support, thus suggesting MSCs as a potential player in these two processes. Finally, in our cohort, 12 patients qualified for TKI discontinuation, and here we observed that all patients who failed TFR had BM fibrosis at diagnosis, further linking fibrosis to LSC persistence. Although we have not investigated whether MF is directly responsible for LSC persistence or whether it is merely an epiphenomenon occurring alongside the development of an LSC-supportive niche, we strongly believe that this is a mechanism that merits further investigation We used microarrays to compare MSCs expression profiles of HD vs. CML patients.

Dataset Information

Differentially Expressed Proteins in Plasma-Derived Extracellular Vesicles from Chronic Myeloid Leukemia Patients

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets