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The two faces of myeloproliferative neoplasms: Molecular events underlying lymphoid transformation

The two faces of myeloproliferative neoplasms: Molecular events underlying lymphoid transformation
The two faces of myeloproliferative neoplasms: Molecular events underlying lymphoid transformation
Multipotent haematopoietic stem cells pass through stages of differentiation with the progressive loss of developmental options leading to the production of terminally differentiated mature blood cells. This process is regulated by soluble cytokines binding to a ligand specific cell surface receptor on a precursor cell. Key to signal transduction are tyrosine kinase proteins which can be divided into two sub families, the receptor protein tyrosine kinases which are transmembrane receptors and retain an intact catalytic kinase domain and the cytoplasmic tyrosine kinases which bind to cytokine receptors. Abnormalities of tyrosine kinase proteins are well recognised in myeloid malignancies, mutation in the cytoplasmic tyrosine kinase JAK2 (V617F) is key in the pathogenesis of myeloproliferative neoplasms, and translocations involving ABL key in the development of chronic myeloid leukaemia. However tyrosine kinase mutations are increasingly recognised to play a role in the pathogenesis of a wider range of haematological cancers. This review focuses on the role of deregulated tyrosine kinase genes either as part of novel fusion proteins involving FGFR1, PDGFR?, PDGFR?, JAK2 and ABL, or as a consequence of point mutation in JAK1 or JAK2 in the development of precursor T and B lymphoid malignancies or mixed myeloid/lymphoid disorders. We also set out some of the postulated mechanisms which underlie the association of tyrosine kinase mutations with the development of lymphoid malignancy.

tyrosine kinase, fgfr1, jak2, lymphoblastic leukaemia, 8p11
0145-2126
1279-1285
Holroyd, Ailsa
2ac6cabb-0f8d-49fd-ab15-bf7cb0c73a36
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Macdonald, Donald H.
1027050f-3c89-4ffb-9517-750761fe3384
Holroyd, Ailsa
2ac6cabb-0f8d-49fd-ab15-bf7cb0c73a36
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Macdonald, Donald H.
1027050f-3c89-4ffb-9517-750761fe3384

Holroyd, Ailsa, Cross, Nicholas C.P. and Macdonald, Donald H. (2011) The two faces of myeloproliferative neoplasms: Molecular events underlying lymphoid transformation. Leukemia Research, 35 (10), 1279-1285. (doi:10.1016/j.leukres.2011.05.037). (PMID:21722956)

Record type: Article

Abstract

Multipotent haematopoietic stem cells pass through stages of differentiation with the progressive loss of developmental options leading to the production of terminally differentiated mature blood cells. This process is regulated by soluble cytokines binding to a ligand specific cell surface receptor on a precursor cell. Key to signal transduction are tyrosine kinase proteins which can be divided into two sub families, the receptor protein tyrosine kinases which are transmembrane receptors and retain an intact catalytic kinase domain and the cytoplasmic tyrosine kinases which bind to cytokine receptors. Abnormalities of tyrosine kinase proteins are well recognised in myeloid malignancies, mutation in the cytoplasmic tyrosine kinase JAK2 (V617F) is key in the pathogenesis of myeloproliferative neoplasms, and translocations involving ABL key in the development of chronic myeloid leukaemia. However tyrosine kinase mutations are increasingly recognised to play a role in the pathogenesis of a wider range of haematological cancers. This review focuses on the role of deregulated tyrosine kinase genes either as part of novel fusion proteins involving FGFR1, PDGFR?, PDGFR?, JAK2 and ABL, or as a consequence of point mutation in JAK1 or JAK2 in the development of precursor T and B lymphoid malignancies or mixed myeloid/lymphoid disorders. We also set out some of the postulated mechanisms which underlie the association of tyrosine kinase mutations with the development of lymphoid malignancy.

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More information

Accepted/In Press date: 1 July 2011
Published date: October 2011
Keywords: tyrosine kinase, fgfr1, jak2, lymphoblastic leukaemia, 8p11

Identifiers

Local EPrints ID: 193863
URI: http://eprints.soton.ac.uk/id/eprint/193863
ISSN: 0145-2126
PURE UUID: 9decc2aa-69e2-4300-94ff-257f85c57fd2
ORCID for Nicholas C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 21 Jul 2011 08:59
Last modified: 15 Mar 2024 03:11

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Author: Ailsa Holroyd
Author: Donald H. Macdonald

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