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Supplementary methods from JAM-C Identifies Src Family Kinase-Activated Leukemia-Initiating Cells and Predicts Poor Prognosis in Acute Myeloid Leukemia

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posted on 2023-03-31, 01:04 authored by Maria De Grandis, Florence Bardin, Cyril Fauriat, Christophe Zemmour, Abdessamad El-Kaoutari, Arnauld Sergé, Samuel Granjeaud, Laurent Pouyet, Camille Montersino, Anne-Sophie Chretien, Marie-Joelle Mozziconacci, Remy Castellano, Ghislain Bidaut, Jean-Marie Boher, Yves Collette, Stéphane J.C. Mancini, Norbert Vey, Michel Aurrand-Lions

Supplementary methods describing flow-cytometry, cumulative relapse incidence calculation and mass spectrometry.

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ARC

SIRIC

Fondation de France

PRT-K

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ARTICLE ABSTRACT

Acute myeloid leukemia (AML) originates from hematopoietic stem and progenitor cells that acquire somatic mutations, leading to disease and clonogenic evolution. AML is characterized by accumulation of immature myeloid cells in the bone marrow and phenotypic cellular heterogeneity reflective of normal hematopoietic differentiation. Here, we show that JAM-C expression defines a subset of leukemic cells endowed with leukemia-initiating cell activity (LIC). Stratification of de novo AML patients at diagnosis based on JAM-C–expressing cells frequencies in the blood served as an independent prognostic marker for disease outcome. Using publicly available leukemic stem cell (LSC) gene expression profiles and gene expression data generated from JAM-C–expressing leukemic cells, we defined a single cell core gene expression signature correlated to JAM-C expression that reveals LSC heterogeneity. Finally, we demonstrated that JAM-C controls Src family kinase (SFK) activation in LSC and that LIC with exacerbated SFK activation was uniquely found within the JAM-C–expressing LSC compartment. Cancer Res; 77(23); 6627–40. ©2017 AACR.

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    Cancer Research

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    Keywords

    Cell SignalingCell adhesionHematological CancersLeukemiasStem Cell Biology

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