MPL515 mutations in myeloproliferative and other myeloid disorders

A study of 1182 patients

Animesh D. Pardanani, Ross L. Levine, Terra Lasho, Yana Pikman, Ruben Mesa, Martha Wadleigh, David P. Steensma, Michelle A. Elliott, Alexandra P. Wolanskyj, William J. Hogan, Rebecca F. McClure, Mark R. Litzow, D. Gary Gilliland, Ayalew Tefferi

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)3472-3476
Number of pages5
JournalBlood
Volume108
Issue number10
DOIs
StatePublished - Nov 15 2006
Externally publishedYes

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Primary Myelofibrosis
Essential Thrombocythemia
Mutation
Polycythemia Vera
Alleles
DNA
Testing
Leukemia, Myelomonocytic, Chronic
Blast Crisis
Myelodysplastic Syndromes
Acute Myeloid Leukemia

ASJC Scopus subject areas

  • Hematology

Cite this

Pardanani, A. D., Levine, R. L., Lasho, T., Pikman, Y., Mesa, R., Wadleigh, M., ... Tefferi, A. (2006). MPL515 mutations in myeloproliferative and other myeloid disorders: A study of 1182 patients. Blood, 108(10), 3472-3476. https://doi.org/10.1182/blood-2006-04-018879

MPL515 mutations in myeloproliferative and other myeloid disorders : A study of 1182 patients. / Pardanani, Animesh D.; Levine, Ross L.; Lasho, Terra; Pikman, Yana; Mesa, Ruben; Wadleigh, Martha; Steensma, David P.; Elliott, Michelle A.; Wolanskyj, Alexandra P.; Hogan, William J.; McClure, Rebecca F.; Litzow, Mark R.; Gilliland, D. Gary; Tefferi, Ayalew.

In: Blood, Vol. 108, No. 10, 15.11.2006, p. 3472-3476.

Research output: Contribution to journalArticle

Pardanani, AD, Levine, RL, Lasho, T, Pikman, Y, Mesa, R, Wadleigh, M, Steensma, DP, Elliott, MA, Wolanskyj, AP, Hogan, WJ, McClure, RF, Litzow, MR, Gilliland, DG & Tefferi, A 2006, 'MPL515 mutations in myeloproliferative and other myeloid disorders: A study of 1182 patients', Blood, vol. 108, no. 10, pp. 3472-3476. https://doi.org/10.1182/blood-2006-04-018879
Pardanani, Animesh D. ; Levine, Ross L. ; Lasho, Terra ; Pikman, Yana ; Mesa, Ruben ; Wadleigh, Martha ; Steensma, David P. ; Elliott, Michelle A. ; Wolanskyj, Alexandra P. ; Hogan, William J. ; McClure, Rebecca F. ; Litzow, Mark R. ; Gilliland, D. Gary ; Tefferi, Ayalew. / MPL515 mutations in myeloproliferative and other myeloid disorders : A study of 1182 patients. In: Blood. 2006 ; Vol. 108, No. 10. pp. 3472-3476.
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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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T1 - MPL515 mutations in myeloproliferative and other myeloid disorders

T2 - A study of 1182 patients

AU - Pardanani, Animesh D.

AU - Levine, Ross L.

AU - Lasho, Terra

AU - Pikman, Yana

AU - Mesa, Ruben

AU - Wadleigh, Martha

AU - Steensma, David P.

AU - Elliott, Michelle A.

AU - Wolanskyj, Alexandra P.

AU - Hogan, William J.

AU - McClure, Rebecca F.

AU - Litzow, Mark R.

AU - Gilliland, D. Gary

AU - Tefferi, Ayalew

PY - 2006/11/15

Y1 - 2006/11/15

N2 - 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.

AB - 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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U2 - 10.1182/blood-2006-04-018879

DO - 10.1182/blood-2006-04-018879

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JO - Blood

JF - Blood

SN - 0006-4971

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