Platelet Derived Growth Factor Expression, Myelofibrosis and Chronic Myelogenous Leukemia

Abstract

CML is often associated with myelofibrosis, and fibrosis in the accelerated phase is one of the diagnostic criteria for this accelerated phase. In this review, the mechanism of myelofibrosis associated with CML is discussed with emphasis on the cell origin of the production and release of platelet derived growth factor (PDGF) and its interaction with marrow fibroblasts. In the initial stage of myelofibrosis in chronic phase CML, atypical small megakaryocytes might leak PDGF, possibly PDGF-AB, together with other growth factors. As the clinical phase of the disease progresses to accelerated or blastic phase, a larger quantity of PDGF-AB or PDGF-BB might be secreted from blastic cells with myeloid phenotype. In addition some fibroblasts may be attracted by the PDGF and proliferate, and deposit collagen as well as fibronectin in the bone marrow stroma.

Marrow fibrosis and its relevance during imatinib treatment of chronic myeloid leukemia

“…Since the ability of a CML clone to induce MF is not a consequence of its quantity, but of its ability to produce other growth factors, particularly platelet-derived growth factor-a/-b or transforming growth factor-b, 8 this finding should not be a surprise. Even in the case of a major molecular response, a focus with 40-90 bcr-abl-positive cells may be expected within the 10 5 marrow cells of a marrow biopsy section, which may be enough to induce a focus with fiber increase.…”

“…[2][3][4] Besides inhibiting bcr/abl-induced increase in tyrosine kinase activity, it also inhibits the platelet-derived growth factor receptor protein kinase a and b 5,6 and the stimulation of c-Abl kinase activity by transforming growth factor-b, 7 cytokines that are important mediators of fibrogenesis in CML. 8 This inhibition is relevant since marrow fibrosis (MF) is a typical complication of CML [9][10][11][12] that correlates with an unfavorable course of disease. 10,12,13 Indeed, reversal of fibrosis was observed in initial studies on imatinib treatment in CML and chronic eosinophilic leukemia with rather small number of patients.…”

Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

“…This is believed to be a consequence of the ability of the chronic myelogenous leukemia clone to produce fibrogenic cytokines even when the quantity of the clone is below the threshold of cytogenetic or molecular detection. 53,56 Importantly emerging or relapsing abnormal fiber increase was an independent predictor of failure of imatinib treatment. Advanced BMF in chronic myelogenous leukemia has also been associated with an increased risk of developing accelerated phase and blast phase disease.…”

Effects of interferon and hydroxyurea on bone marrow fibrosis in chronic myelogenous leukaemia: a comparative retrospective multicentre histological and clinical study

“…Because pathogenesis of myelo®brosis is closely linked with the release of certain growth factors from megakaryocytes (Kimura et al, 1995;Martyre Â, 1995), this cell lineage was also taken into consideration. .…”