MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients

Blood - Tập 108 Số 10 - Trang 3472-3476 - 2006
Animesh Pardanani1, Ross L. Levine1, Terra L. Lasho1, Yana Pikman1, Ruben A. Mesa1, Martha Wadleigh1, David P. Steensma1, Michelle A. Elliott1, Alexandra P. Wolanskyj1, William J. Hogan1, Rebecca F. McClure1, Mark R. Litzow1, D. Gary Gilliland1, Ayalew Tefferi1
1From the Divisions of Hematology and Hematopathology, Mayo Clinic, Rochester, MN; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and the Howard Hughes Medical Institute, Harvard Medical School, Boston, MA.

Tóm tắt

Abstract Recently, a gain-of-function MPL mutation, MPLW515L, was described in patients with JAK2V617F-negative myelofibrosis with myeloid metaplasia (MMM). To gain more information on mutational frequency, disease specificity, and clinical correlates, genomic DNA from 1182 patients with myeloproliferative and other myeloid disorders and 64 healthy controls was screened for MPL515 mutations, regardless of JAK2V617F mutational status: 290 with MMM, 242 with polycythemia vera, 318 with essential thrombocythemia (ET), 88 with myelodysplastic syndrome, 118 with chronic myelomonocytic leukemia, and 126 with acute myeloid leukemia (AML). MPL515 mutations, either MPLW515L (n = 17) or a previously undescribed MPLW515K (n = 5), were detected in 20 patients. The diagnosis of patients with mutant MPL alleles at the time of molecular testing was de novo MMM in 12 patients, ET in 4, post-ET MMM in 1, and MMM in blast crisis in 3. Six patients carried the MPLW515L and JAK2V617F alleles concurrently. We conclude that MPLW515L or MPLW515K mutations are present in patients with MMM or ET at a frequency of approximately 5% and 1%, respectively, but are not observed in patients with polycythemia vera (PV) or other myeloid disorders. Furthermore, MPL mutations may occur concurrently with the JAK2V617F mutation, suggesting that these alleles may have functional complementation in myeloproliferative disease.

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Tài liệu tham khảo

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Thông tin xuất bản

Blood

Tập 108 Số 10

3472-3476

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