title: Development of chronic myeloid leukaemia in patients treated with anti-VEGF therapies for clear cell renal cell cancer.
abstract: Tyrosine kinase inhibitors are novel therapies targeting specific cellular signalling pathways. Sunitinib and sorafenib primarily block tyrosine kinase receptors involved in the progression of many tumours, including clear cell renal cell cancer (ccRCC). Although developed to target selected receptors, it is becoming apparent that they inhibit other kinases; this may result in the development of unexpected side effects. This is potentially dangerous as kinases on noncancerous cells are also inhibited. TKI off-target effects contributing to cardiotoxicity, hypothyroidism, hypertension, fatigue, hair depigmentation, hand-foot syndrome and gastrointestinal perforation have been described. We report three patients (3/412) treated with sunitinib and sorafenib who developed chronic myeloid leukaemia (CML) during treatment for ccRCC, proposing a molecular mechanism of tyrosine kinase inhibitors action on bone marrow cells that might be co-responsible for CML development.
authors: Department of Oncology with Laboratory of Molecular Oncology, Military Institute of Medicine, Warsaw, Poland.
authors: Anna M
authors: AM
authors: Czarnecka
authors: Sylwia
authors: S
authors: Oborska
authors: Piotr
authors: P
authors: Rzepecki
authors: Cezary
authors: C
authors: Szczylik
mesh_terms: D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000009:adverse effects; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000009:adverse effects; D011758:Pyrroles / Q000009:adverse effects; D000077157:Sorafenib; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib
keywords: CML; RCC; clear cell renal cell; renal cell cancer; sorafenib; sunitinib; tyrosine kinase carcinoma