Myelofibrosis and acute megakaryoblastic leukemia in a child: Topographic relationship between fibroblasts and megakaryocytes with an α-granule defect

A prospective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): Children's Oncology Group (COG) study POG-9481

“…48 Alternatively, the presence of megakaryoblastic infiltration may lead to release of cytokines (platelet-derived growth factor and transforming growth factor ␤), which are known to induce fibrosis. 49,50 In contrast, infants who subsequently developed acute leukemia were commonly asymptomatic at birth. Progression to leukemia was significantly associated with additional karyotypic abnormalities in addition to trisomy 21 at time of diagnosis of TL.…”

Mixed Myelodysplastic Syndrome and Myeloproliferative Disorder with Bone Marrow and Pulmonary Fibrosis: The Role of Megakaryocytes

“…Moreover, in megakaryocytic or hairy cell leukaemias, there is general agreement that myelofibrosis represents a constant clinicopathological feature. Acquired abnormal platelet granule storage with increased secretion either of PGDF or PF-4 was described [3, 4]. After treatment, the remission of leukaemias with disappearance of myelofibrosis was associated with the normalization of platelet abnormalities, favouring the relationship between the abnormal platelet granule storage and myelofibrosis [3, 4].…”

“…Thus, most of the myeloproliferative disorders can evolve towards a myelofibrosis [2]. Megakaryocytic and hairy cell leukaemias are also associated with myelofibrosis [3, 4]. Less frequently, bone marrow fibrosis can be found in MDS [5].…”

Unique Myeloid Leukemias in Young Children with Down Syndrome: Cell Origin, Association with Hematopoietic Microenvironment and Leukemogenesis

“…4c, d), but not myelofibrosis (Becroft & Zwi, 1990;Ruchelli et al, 1991;Miyauchi et al, 1992;Yagihashi et al, 1995;Schwab et al, 1998;Shiozawa et al, 2004). It has been shown that leukemic blasts in AMKL produce cytokines, including platelet-derived growth factor (PDGF), platelet factor 4 and transforming growth factor β (TGFβ) that stimulate fibroblasts in the bone marrow causing myelofibrosis (Breton-Gorius et al, 1982;Roberts et al, 1986;Sunami et al, 1987;Terui et al, 1990). Since blasts in TL have features similar to those of megakaryoblasts in AMKL-DS and TL is a disorder of neonates and fetuses, it appears that TL is a very unusual form of neoplasia originating from the fetal liver, the major organ of hematopoiesis during the fetal stage, and that leukemic blasts that arise in the fetal liver produce cytokines that stimulate fibroblasts to induce liver fibrosis in the same manner as myelofibrosis in AMKL-DS.…”