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

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 functional deficiencies of iNKT cells that are restored upon remission. These results suggest a possible contribution to disease control by TK inhibitor therapies.

journal_name

Eur J Immunol

authors

Rossignol A,Levescot A,Jacomet F,Robin A,Basbous S,Giraud C,Roy L,Guilhot F,Turhan AG,Barra A,Herbelin A,Gombert JM

doi

10.1002/eji.201142043

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

1870-5

issue

7

eissn

0014-2980

issn

1521-4141

journal_volume

42

pub_type

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