Leukocytosis, mild anemia, thrombocytosis, and panhyperplasia in the marrow characterize the early stages of most of the CMPD, whereas extramedullary hematopoiesis (such as in the spleen or liver), peripheral cytopenias (anemia, leukopenia, or thrombocytopenia), and myelofibrosis, with or without osteosclerosis, reflect the changes seen in the later stages.
Hematologic, cytogenetic, and molecular studies demonstrated the heterogeneity of such cases, including the first example of clinically typical myelofibrosis (MF) associated with a bcr gene rearrangement characteristic of chronic myelogenous leukemia (CML).
Culture for 72 h with G-CSF or GM-CSF disclosed a minor abnormal clone which was undetected in 24 and 48 h cultures in a patient with myelofibrosis with myeloid metaplasia.
The purpose of this study is to evaluate the incidence of MDR-1 expression in MMM using a highly sensitive polymerase chain reaction (PCR)-based assay.
The purpose of this study is to evaluate the incidence of MDR-1 expression in MMM using a highly sensitive polymerase chain reaction (PCR)-based assay.
Our data show that molecular deletions of 13q14 are detected in a relatively large fraction of BCR/ABL- CMPD (38%), that they appear to be more frequent in MMM than in other BCR/ABL- CMPD, and that they may be present at diagnosis or occur during blastic evolution of the neoplasia.
The expression of c-kit receptor (c-kit R; CD117) and CD34 was examined in acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML) in blastic transformation (BT), and myelofibrosis (MF) in myeloid BT.
The expression of c-kit receptor (c-kit R; CD117) and CD34 was examined in acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML) in blastic transformation (BT), and myelofibrosis (MF) in myeloid BT.
In the first case (female, aged 65, in blastic transformation which developed one year after the initial diagnosis of myelofibrosis), a t(14;22) (q32;q11) was found in association with several other chromosomal abnormalities [48,XX,+X,+5,del(5) (q12q32),+8,der(9)t(9;11)(q32;q11),-11]; molecular analysis demonstrated the presence of a BCR-ABL chimeric gene and mRNA transcript of the b2-a2 type.
Actually, the increased expression of bFGF and its receptors associated with the reduction of the TGF-beta binding receptor in CD34+ progenitors from MMM patients might facilitate the expansion of hematopoietic progenitors, not only by stimulating their growth and/or survival, but also by overcoming negative regulatory signals.
Previous results from our group have shown an increased production of two potent fibrogenic factors also involved in the regulation of primitive hematopoietic cells, namely transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF), in patients with MMM.
Actually, the increased expression of bFGF and its receptors associated with the reduction of the TGF-beta binding receptor in CD34+ progenitors from MMM patients might facilitate the expansion of hematopoietic progenitors, not only by stimulating their growth and/or survival, but also by overcoming negative regulatory signals.
Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.
At 30 days after therapy bone marrow and spleen of mice treated with AdCMV.TPO were populated with a large number of polyploid megakaryocytes, but there was no evidence of circulating megakaryocytes in the liver or lungs and no pathologic bone abnormalities such as osteosclerosis or myelofibrosis.
Studies of p16 alterations with homozygous deletions and mutation analysis were done in 32 patients with agnogenic myeloid metaplasia (AMM) including six patients in leukemic phase.
Studies of p16 alterations with homozygous deletions and mutation analysis were done in 32 patients with agnogenic myeloid metaplasia (AMM) including six patients in leukemic phase.
Our results suggest the possibility of a novel gene, distinct from ZNF198, that is located at chromosome 13q12 and involved in the pathogenesis of myelofibrosis.
We describe a variant form, French-American-British (FAB) M3v, of acute promyelocytic leukemia (APL; FAB M3) with atypical morphocytochemical features, immature antigens (CD34 and HLA-DR) and marked myelofibrosis (MF).
In a prospective study of 42 patients with myelofibrosis with myeloid metaplasia (MMM), peripheral blood (PB) and bone marrow (BM) interphase cytogenetics and PB CD34 enumeration were performed concomitantly with BM karyotype analysis.
Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis.
This study suggests that SP may be implicated in the pathophysiology of myelofibrosis, though its role would have to be substantiated in future research.(Blood.2001;97:3025-3031)
In addition, we propose that the emperipolesis was caused by increased P-selectin in megakaryocytes, and resulted in release of fibroblastic growth factors, explaining the myelofibrosis.