Journal article

Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm

Philip A Beer, Francois Delhommeau, Jean-Pierre LeCouedic, Mark A Dawson, Edwin Chen, David Bareford, Rajko Kusec, Mary Frances McMullin, Claire N Harrison, Alessandro M Vannucchi, William Vainchenker, Anthony R Green

BLOOD | AMER SOC HEMATOLOGY | Published : 2010


Acute myeloid leukemia (AML) may follow a JAK2-positive myeloproliferative neoplasm (MPN), although the mechanisms of disease evolution, often involving loss of mutant JAK2, remain obscure. We studied 16 patients with JAK2-mutant (7 of 16) or JAK2 wild-type (9 of 16) AML after a JAK2-mutant MPN. Primary myelofibrosis or myelofibrotic transformation preceded all 7 JAK2-mutant but only 1 of 9 JAK2 wild-type AMLs (P = .001), implying that JAK2-mutant AML is preceded by mutation(s) that give rise to a "myelofibrosis" phenotype. Loss of the JAK2 mutation by mitotic recombination, gene conversion, or deletion was excluded in all wild-type AMLs. A search for additional mutations identified alterati..

View full abstract


Awarded by Cancer Research UK

Awarded by Medical Research Council

Funding Acknowledgements

This work was supported by the UK Medical Research Council, the Leukaemia Research Fund, the Kay Kendall Leukaemia Fund, the NIHR Cambridge Biomedical Research Centre, the Leukemia & Lymphoma Society of America, the Myeloproliferative Disorders Foundation, the Laurette Fugain Association, the Fondation de France, the Ligue Nationale Contre le Cancer, and the Canceropole Ile de France.