Evidence for BCR-ABL-dependent dysfunctions of iNKT cells from chronic myeloid leukemia patients

European Journal of Immunology
Alexis RossignolJean-Marc Gombert

Abstract

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem-cell malignancy characterized by the presence of the chimeric BCR-ABL oncoprotein with deregulated tyrosine-kinase (TK) activity. Although conventional T cells are acknowledged as important players in the control of CML, a possible modification of invariant NKT (iNKT) cells, known for their antitumoral activity, has not been established as yet. Here, we showed that the expression of perforin, CD95L, and promyelocytic leukemia zinc finger, a transcription factor required for maintenance of iNKT cell functions, was reduced or suppressed in CML patients at diagnosis, as compared with healthy individuals. The proliferation rate of blood iNKT cells in response to their cognate ligand was likewise diminished. These functional deficiencies were corrected in patients having achieved complete cytogenetic remission following TK inhibitor or IFN-α therapy. iNKT cells from CML patients in the chronic phase did not display increased TK activity, which argued against a direct autonomous action of BCR-ABL. Instead, we found that their anergic status originated from both intrinsic and APC-dependent dysfunctions. Our data demonstrate that chronic phase CML is associated with function...Continue Reading

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Citations

Jan 7, 2014·Current Hematologic Malignancy Reports·Mette IlanderSatu Mustjoki
Apr 24, 2015·European Journal of Immunology·Florence JacometJean-Marc Gombert
Dec 5, 2017·Médecine sciences : M/S·Alice BarbarinJean-Marc Gombert
Mar 3, 2015·Expert Review of Clinical Immunology·Vladimír Vonka, Martina Petráčková
Apr 12, 2017·Frontiers in Immunology·Alice BarbarinJean-Marc Gombert
May 16, 2017·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Emilie Cayssials, Francois Guilhot
Nov 7, 2019·Frontiers in Immunology·Jani-Sofia AlmeidaPaulo Rodrigues-Santos
Jan 29, 2021·Journal of Immunology Research·Nilberto Dias de AraújoAllyson Guimarães Costa
Aug 28, 2021·Journal of Personalized Medicine·Paulina Kwaśnik, Krzysztof Giannopoulos

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