Evaluation of JAK2 in B and T cell neoplasms: identification of JAK2(V617F) mutation of undetermined significance (JMUS) in the bone marrow of three individuals.

BACKGROUND/AIMS: The JAK2(V617F) mutation, which has been found in patients with myeloproliferative disorders (MPD), has not yet been evaluated in lymphoproliferative disorders by any adequately sensitive techniques.

METHODS: We investigated whether low levels of JAK2(V617F) are present in lymphoid neoplasms using a highly sensitive and highly specific amplification refractory mutation system PCR (ARMS-PCR) assay.

RESULTS: While 234 of 237 cases did not carry the JAK2(V617F) allele, it was identified in the bone marrow of 3 B cell lymphoma patients. The mutation was found to be neither associated with the lymphomas per se, nor with any signs, symptoms or laboratory findings of MPD. Moreover, JAK2(V617F) appeared subsequently in the peripheral blood of 2 of the 3 patients.

CONCLUSION: These findings suggest that JAK2(V617F) arises in the bone marrow of individuals before clinical manifestation of any myeloid disorders. Presence of JAK2(V617F) in bone marrow might therefore increase the risk of future MPD development, just as monoclonal gammopathy of undetermined significance (MGUS) increases the risk of multiple myeloma. We term this phenomenon 'JAK2(V617F) of undetermined significance' (JMUS). Its clinical significance remains to be determined. To our knowledge, these findings represent the first identification of JAK2(V617F) in the bone marrow of patients without myeloid malignancies.