Signal transduction therapy in haematological malignancies: identification and targeting of tyrosine kinases

Chase, Andrew and Cross, Nicholas C.P. (2006) Signal transduction therapy in haematological malignancies: identification and targeting of tyrosine kinases. Clinical Science, 111 (4), 233-249. (doi:10.1042/CS20060035).

Abstract

Tyrosine kinases play key roles in cell proliferation, survival and differentiation. Their aberrant activation, caused either by the formation of fusion genes by chromosome translocation or by intragenic changes, such as point mutations or internal duplications, is of major importance in the development of many haematological malignancies. An understanding of the mechanisms by which BCR-ABL contributes to the pathogenesis of chronic myeloid leukaemia led to the development of imatinib, the first of several tyrosine kinase inhibitors to enter clinical trials. Although the development of resistance has been problematic, particularly in aggressive disease, the development of novel inhibitors and combination with other forms of therapy shows promise.
Abbreviations: ALK, anaplastic lymphoma kinase; ALL, acute lymphoblastic leukaemia; AML, acute myeloid leukaemia; CEL, chronic eosinophilic leukaemia; CML, chronic myeloid leukaemia; CMML, chronic myelomonocytic leukaemia; EGFR, epidermal growth factor receptor; EMS, Eight p11 myeloproliferative syndrome; EPO, erythropoietin; FGFR, fibroblast growth factor receptor; FIP1L1, Fip1-like 1; FLT3, Fms-like tyrosine kinase 3; FISH, fluorescence in situ hybridization; HES, hypereosinophilic syndrome; IFNa, interferon a; IL3, interleukin 3; IRIS, International Randomized study of Interferon and STI571; ITD, internal tandem duplication; JAK, Janus kinase; MDS, myelodysplastic syndrome; MPD, myeloproliferative disorder; NTRK, neurotrophin receptor kinase; PDGFR, platelet-derived growth factor receptor; Ph, Philadelphia chromosome; PV, polycythaemia vera; RT, reverse transcription; SCT, stem cell transplantation; TK, tyrosine kinase.

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Contributors

Author: Andrew Chase

Author: Nicholas C.P. Cross

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