Defective erythropoiesis in primary myelofibrosis associated with a chromosome 11 abnormality

Abstract

Summary A case of primary myelofibrosis was identified with a previously unreported complex karyotype with two abnormal clones in addition to a proportion of normal cells: 46,XY, -2, -1 1, + der(2)t(2; 1) (q24/31;q13), + mar and 45,XY, -2, -1 1, + der(2)t(2;1 1)(q24/31;q13), + mar, -17,del(7q). Study of circulating committed progenitors from this patient consistently showed (1) an absence of erythroid progenitors which is uncommon and (2) greatly increased granulocyte-monocyte progenitors (CFU-GM) which is generally observed in myelofibrosis. Further study showed that peripheral blood mononuclear cells co-cultured with irradiated normal bone marrow stroma generated increased numbers of CFU-GM compared with controls but failed to generate erythroid progenitors, providing evidence for an intrinsic defect in erythropoiesis. Only once previously has the absence of erythroid progenitors in primary myelofibrosis been studied in relation to cytogenetic abnormalities. This case also revealed a complex karyotype which, however, shared with our case a defect on chromosome 11. The identification of two cases of primary myelofibrosis which lack committed erythroid progenitor cells and which show in common a chromosomal defect on chromosome 11 point to the existence of genes on this chromosome which play a key role during erythropoiesis.

Pathogenetic insight and prognostic information from standard and molecular cytogenetic studies in the BCR-ABL-negative myeloproliferative neoplasms (MPNs)

“…150 Structural abnormalities of the long arm of chromosome 12, non-random findings in myelofibrosis, confers a poor prognosis because of early blast transformation, 151 whereas Strasser-Weipel et al 152 reported the poor prognosis of chromosome 7 deletions (À7/7qÀ), although somewhat surprisingly this was not related to leukaemic transformation. Patten et al 153 have reported an association between a lack of committed erythroid progenitor cells in PMF and chromosome 11 abnormalities and suggested the existence of genes on this chromosome which has an important function during erythropoiesis.…”

Cytogenetic and Molecular Genetic Aspects of Idiopathic Myelofibrosis

“…Trisomy 13, a non-random aberration in myelofibrosis [70], confers a poor prognosis due to early blast transformation [71, 72], as appears to be the case for der(1)t(1;9) [62]and t(6;10) (q27;q11) [73]. Patton et al [74]have reported an association between a lack of committed erythroid progenitor cells in idiopathic myelofibrosis and chromosome 11 abnormalities and suggested the existence of genes on this chromosome which play a key role during erythropoiesis.…”