Targeted therapies in myeloid leukemia.
Targeted therapies for hematological malignancies have come of age since the advent of all trans retinoic acid (ATRA) for treating APL and STI571/Imatinib Mesylate/Gleevec for CML. There are good molecular targets for other malignancies and several new drugs are in clinical trials. In this review, we will concentrate on individual abnormalities that exist in the myelodysplastic syndromes (MDS) and myeloid leukemias that are targets for small molecule therapies (summarised in Fig. 1). We will cover fusion proteins that are produced as a result of translocations, including BCR-ABL, the FLT3 tyrosine kinase receptor and RAS. Progression of diseases such as MDS to secondary AML occur as a result of changes in the balance between cell proliferation and apoptosis and we will review targets in both these areas, including reversal of epigenetic silencing of genes such as p15(INK4B).
John
Alison M
AM
Leukaemia Sciences Laboratories, Department of Haematological Medicine, Guy's, King's and St Thomas' School of Medicine, King's College London, The Rayne Institute, 123 Coldharbour Lane, London SE5 9NU, UK.
Thomas
N Shaun B
NS
Mufti
Ghulam J
GJ
Padua
Rose Ann
RA
D000818:Animals; D002455:Cell Division; D020868:Gene Silencing; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics
D006133:Growth Substances; D011518:Proto-Oncogene Proteins