Is JAK2 Inducible by Cytotoxic Chemotherapy?

The JAK2^V617F mutation accounts for most cases of myeloproliferative neoplasms (MPN). Only a few case reports of MPN following cytotoxic chemotherapy have been reported, and all of them were published prior to the discovery of the JAK2^V617F mutation. We report a series of 6 patients who developed a JAK2^V617F positive MPN following cytotoxic chemotherapy.

From 2006 to 2009, 6 patients with a history of a hematologic or an oncologic malignancy who developed an MPN were identified and their medical records retrospectively reviewed. One patient had acute lymphoblastic leukemia, 1 had Hodgkin lymphoma, 1 had squamous cell carcinoma of the head and neck, 1 had cervical cancer, and 2 had breast cancer. All patients were in remission from their primary malignancies at the time the MPN was diagnosed. Five were females. The median age at diagnosis was 72 years. Median time to development of the myeloproliferative neoplasm was 14 years. Type of chemotherapy exposure, MPN diagnosis and time to MPN in each case is shown in the table below. The JAK2^V617F mutation was detected either in the peripheral blood or the bone marrow of all patients. There was no predominance of any specific MPN diagnosis. Patients who received platinum-based chemotherapy developed the MPN sooner than those who received alkylators (6 vs 17.5 years respectively). Treatment consisted of phlebotomy, hydroxyurea, anagrelide, aspirin or a combination as deemed appropriate by the treating hematologist.

These findings lead us to hypothesize whether the development of JAK2^V617F positive MPN may be related to prior exposure to cytotoxic chemotherapy. Exposure to platinum-based chemotherapy may cause the disorder to appear sooner compared with exposure to alkylators. Recently, JAK2^V617F positive MPN was found to be strongly associated with a specific constitutional haplotype, 46/1¹ suggesting increased susceptibility to this mutation. Chromosomal analyses are planned to show whether any of the reported patients exhibit this haplotype.

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Ref: 1.Jones et al, Nat Genet. 2009 Apr;41(4):446-9. 2009 Mar 15.

The authors have no relevant disclosure.

No relevant conflicts of interest to declare.