Molecular mechanisms associated with leukemic transformation of MPL-mutant myeloproliferative neoplasms

Philip A Beer, Christina A Ortmann, Frank Stegelmann, Paola Guglielmelli, John T Reilly, Thomas Stauffer Larsen, Hans C Hasselbalch, Alessandro M Vannucchi, Peter Möller, Konstanze Döhner, Anthony R Green

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Somatic activating mutations in MPL, the thrombopoietin receptor, occur in the myeloproliferative neoplasms, although virtually nothing is known about their role in evolution to acute myeloid leukemia. In this study, the MPL T487A mutation, identified in de novo acute myeloid leukemia, was not detected in 172 patients with a myeloproliferative neoplasm. In patients with a prior MPL W515L-mutant myeloproliferative neoplasm, leukemic transformation was accompanied by MPL-mutant leukemic blasts, was seen in the absence of prior cytoreductive therapy and often involved loss of wild-type MPL by mitotic recombination. Moreover, clonal analysis of progenitor colonies at the time of leukemic transformation revealed the presence of multiple genetically distinct but phylogenetically-related clones bearing different TP53 mutations, implying a mutator-phenotype and indicating that leukemic transformation may be preceded by the parallel expansion of diverse hematopoietic clones.
OriginalsprogEngelsk
TidsskriftHaematologica
Vol/bind95
Udgave nummer12
Sider (fra-til)2153-6
Antal sider4
ISSN0390-6078
DOI
StatusUdgivet - 1. dec. 2010

Fingeraftryk

Acute Myeloid Leukemia
Mutation
Clone Cells
Thrombopoietin Receptors
Neoplasms

Citer dette

Beer, P. A., Ortmann, C. A., Stegelmann, F., Guglielmelli, P., Reilly, J. T., Larsen, T. S., ... Green, A. R. (2010). Molecular mechanisms associated with leukemic transformation of MPL-mutant myeloproliferative neoplasms. Haematologica, 95(12), 2153-6. https://doi.org/10.3324/haematol.2010.029306
Beer, Philip A ; Ortmann, Christina A ; Stegelmann, Frank ; Guglielmelli, Paola ; Reilly, John T ; Larsen, Thomas Stauffer ; Hasselbalch, Hans C ; Vannucchi, Alessandro M ; Möller, Peter ; Döhner, Konstanze ; Green, Anthony R. / Molecular mechanisms associated with leukemic transformation of MPL-mutant myeloproliferative neoplasms. I: Haematologica. 2010 ; Bind 95, Nr. 12. s. 2153-6.
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title = "Molecular mechanisms associated with leukemic transformation of MPL-mutant myeloproliferative neoplasms",
abstract = "Somatic activating mutations in MPL, the thrombopoietin receptor, occur in the myeloproliferative neoplasms, although virtually nothing is known about their role in evolution to acute myeloid leukemia. In this study, the MPL T487A mutation, identified in de novo acute myeloid leukemia, was not detected in 172 patients with a myeloproliferative neoplasm. In patients with a prior MPL W515L-mutant myeloproliferative neoplasm, leukemic transformation was accompanied by MPL-mutant leukemic blasts, was seen in the absence of prior cytoreductive therapy and often involved loss of wild-type MPL by mitotic recombination. Moreover, clonal analysis of progenitor colonies at the time of leukemic transformation revealed the presence of multiple genetically distinct but phylogenetically-related clones bearing different TP53 mutations, implying a mutator-phenotype and indicating that leukemic transformation may be preceded by the parallel expansion of diverse hematopoietic clones.",
author = "Beer, {Philip A} and Ortmann, {Christina A} and Frank Stegelmann and Paola Guglielmelli and Reilly, {John T} and Larsen, {Thomas Stauffer} and Hasselbalch, {Hans C} and Vannucchi, {Alessandro M} and Peter M{\"o}ller and Konstanze D{\"o}hner and Green, {Anthony R}",
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Beer, PA, Ortmann, CA, Stegelmann, F, Guglielmelli, P, Reilly, JT, Larsen, TS, Hasselbalch, HC, Vannucchi, AM, Möller, P, Döhner, K & Green, AR 2010, 'Molecular mechanisms associated with leukemic transformation of MPL-mutant myeloproliferative neoplasms', Haematologica, bind 95, nr. 12, s. 2153-6. https://doi.org/10.3324/haematol.2010.029306

Molecular mechanisms associated with leukemic transformation of MPL-mutant myeloproliferative neoplasms. / Beer, Philip A; Ortmann, Christina A; Stegelmann, Frank; Guglielmelli, Paola; Reilly, John T; Larsen, Thomas Stauffer; Hasselbalch, Hans C; Vannucchi, Alessandro M; Möller, Peter; Döhner, Konstanze; Green, Anthony R.

I: Haematologica, Bind 95, Nr. 12, 01.12.2010, s. 2153-6.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Molecular mechanisms associated with leukemic transformation of MPL-mutant myeloproliferative neoplasms

AU - Beer, Philip A

AU - Ortmann, Christina A

AU - Stegelmann, Frank

AU - Guglielmelli, Paola

AU - Reilly, John T

AU - Larsen, Thomas Stauffer

AU - Hasselbalch, Hans C

AU - Vannucchi, Alessandro M

AU - Möller, Peter

AU - Döhner, Konstanze

AU - Green, Anthony R

PY - 2010/12/1

Y1 - 2010/12/1

N2 - Somatic activating mutations in MPL, the thrombopoietin receptor, occur in the myeloproliferative neoplasms, although virtually nothing is known about their role in evolution to acute myeloid leukemia. In this study, the MPL T487A mutation, identified in de novo acute myeloid leukemia, was not detected in 172 patients with a myeloproliferative neoplasm. In patients with a prior MPL W515L-mutant myeloproliferative neoplasm, leukemic transformation was accompanied by MPL-mutant leukemic blasts, was seen in the absence of prior cytoreductive therapy and often involved loss of wild-type MPL by mitotic recombination. Moreover, clonal analysis of progenitor colonies at the time of leukemic transformation revealed the presence of multiple genetically distinct but phylogenetically-related clones bearing different TP53 mutations, implying a mutator-phenotype and indicating that leukemic transformation may be preceded by the parallel expansion of diverse hematopoietic clones.

AB - Somatic activating mutations in MPL, the thrombopoietin receptor, occur in the myeloproliferative neoplasms, although virtually nothing is known about their role in evolution to acute myeloid leukemia. In this study, the MPL T487A mutation, identified in de novo acute myeloid leukemia, was not detected in 172 patients with a myeloproliferative neoplasm. In patients with a prior MPL W515L-mutant myeloproliferative neoplasm, leukemic transformation was accompanied by MPL-mutant leukemic blasts, was seen in the absence of prior cytoreductive therapy and often involved loss of wild-type MPL by mitotic recombination. Moreover, clonal analysis of progenitor colonies at the time of leukemic transformation revealed the presence of multiple genetically distinct but phylogenetically-related clones bearing different TP53 mutations, implying a mutator-phenotype and indicating that leukemic transformation may be preceded by the parallel expansion of diverse hematopoietic clones.

U2 - 10.3324/haematol.2010.029306

DO - 10.3324/haematol.2010.029306

M3 - Journal article

VL - 95

SP - 2153

EP - 2156

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 12

ER -