Abstract
Amongst males, leukaemia is the most common cause of cancer-related death in individuals younger than 40 years of age whereas in female children and adolescents, leukaemia is the most common cause of cancer-related death. Chronic myeloid leukaemia (CML) is a chronic leukaemia of the haematopoietic stem cells affecting mostly adults. The disease results from a translocation of the Philadelphia chromosome in stem cells of the bone marrow. CML patients usually present with mild to moderate anaemia and with decreased, normal, or increased platelet counts. CML represents 0.5% of all new cancer cases in the United States (2016). In 2016, an estimated 1070 people would die of this disease in the United States. Platelets serve as a means for tumours to increase growth and to provide physical- and mechanical support to elude the immune system and to metastasize. Currently there is no literature available on the role that platelets play in CML progression, despite literature reporting the fact that platelet count and size are affected. Resistance to CML treatment with tyrosine kinase inhibitors can be as a result of acquired resistance ensuing from mutations in the tyrosine kinase domains, loss of response or poor tolerance. In CML this resistance has recently become linked to bone marrow (BM) angiogenesis which aids in the growth and survival of leukaemia cells. The discovery of the lungs as a site of haematopoietic progenitors, suggests that CML resistance is not localized to the bone marrow and that the mutations leading to the disease and resistance to treatment may also occur in the haematopoietic progenitors in the lungs. In conclusion, platelets are significantly affected during CML progression and treatment. Investigation into the role that platelets play in CML progression is vital including how treatment affects the cell death mechanisms of platelets.
Highlights
Amongst males, leukaemia is the most common cause of cancer-related death in individuals younger than 40 years of age whereas leukaemia is the most common cause of cancer-related death in female children and adolescents [1,2,3]
With the discovery of the lungs as a site of haematopoietic progenitors, this may indicate that chronic myeloid leukaemia (CML) resistance is not localized to the bone marrow and that the mutations leading to the disease and resistance to treatment may occur in the haematopoietic progenitors in the lungs [32]
This may be explained by the fact that both platelet derived growth factor receptors (PDGFRs)-α and PDGFR-β engage in signaling pathways namely rat sarcoma (RAS)-mitogen activated protein kinases (MAPK) and phosphatidylinositol 3-kinase (PI3K) known to be involved in cellular- and developmental responses including stimulation of cell growth, differentiation and migration [49]
Summary
Leukaemia is the most common cause of cancer-related death in individuals younger than 40 years of age whereas leukaemia is the most common cause of cancer-related death in female children and adolescents [1,2,3]. The abnormality differs for each type of leukaemia depending on the genetic mutation present, and results in the lymphocytes or myeloid cells not being able to perform their functions. The latter may not be symptomatic for a prolonged period ranging from months to years [4, 5]. Treatment and survival rates of leukaemia depend on the type of genetic mutation responsible and stage at time of diagnosis (which varies per leukaemia type) These include radiation therapy, chemotherapy, targeted therapy and combinations of the three treatments (Table 3) [7]. This results in these cells being able to evade dependency on growth factors and resistance to harmful effects of drugs and irradiation [6, 9,10,11,12]
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