Exploring polycythaemia vera with fluorescence in situ hybridization: additional cryptic 9p is the most frequent abnormality detected*

Abstract

Summary. Between 1986 and 2001, 220 patients with polycythaemia vera (PV) were studied using conventional cytogenetics. Of 204 evaluable patients, 52 (25AE4%) had clonal abnormalities. The recurrent chromosomal rearrangements were those of chromosome 9 (21AE1%), del(20q) (19AE2%), trisomy 8 (19AE2%), rearrangements of 13q (13AE4%), abnormalities of 1q (11AE5%), and of chromosomes 5 and 7 (9AE6%). Subsequent analysis of 32 patients, performed at follow-up of up to 14AE8 years, revealed new clonal abnormalities in five patients and the disappearance of an abnormal clone in four. Eleven patients remained normal up to 11AE5 years and seven patients maintained an abnormality for over 10 years. Fifty-three patients were studied retrospectively using interphase fluorescence in situ hybridization (I-FISH), utilizing probes for centromere enumeration of chromosomes 8 and 9, and for 13q14 and 20q12 loci. Conventional cytogenetics demonstrated clonal chromosome abnormalities in 23% of these 53 patients. The addition of I-FISH increased the detection of abnormalities to 29% and permitted clarification of chromosome 9 rearrangements in an additional 5AE6% of patients. FISH uncovered rearrangements of chromosome 9 in 53% of patients with an abnormal FISH pattern, which represented the most frequent genomic alteration in this series.

Limited clinical value of regular bone marrow cytogenetic analysis in imatinib-treated chronic phase CML patients monitored by RQ-PCR for BCR-ABL

“…37,38 As loss of the Y chromosome can be found in a significant proportion of older males in the absence of any clonal haematological disorder, the pathological significance of this finding is uncertain. 38 Trisomy 8 was the next most common clonal abnormality and has also been reported in a wide range of other myeloid disorders [39][40][41][42] and in CML patients treated with interferon. 26,40,43,44 It has been postulated that the emergence of trisomy 8 during regression of the CML clone may represent the re-emergence of polyclonal haematopoiesis in a patient with underlying constitutional mosaicism.…”

Phenotypic variations and new mutations in JAK2 V617F–negative polycythemia vera, erythrocytosis, and idiopathic myelofibrosis

“…Polycythemia vera (PV), idiopathic myelofibrosis (IMF) and essential thrombocytosis (ET) are clonal myeloproliferative disorders whose shared features include origin in a multipotent hematopoietic progenitor cell (1), cytogenetic abnormalities of chromosomes 1,8,9,13 and 20 (2), growth factor-independent in vitro hematopoietic colony formation(3) and epigenetic abnormalities, such as increased granulocyte PRV-1 mRNA expression(4) and impaired megakaryocyte and platelet thrombopoietin receptor protein (Mpl) expression (5). Taken together, these shared phenotypic and genotypic features suggest that PV, IMF and ET are pathogenetically related.…”

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

“…Nevertheless, these and other studies suggested that gene(s) on 9p, rather than 9q, are crucial to the pathogenesis of PV. 93 In an attempt to clarify further the genomic regions that cause the PV phenotype, Kralovics et al 94 carried out a genome-wide microsatellite screen for LOH. Three genomic regions were identified on chromosomes 9p, 10q and 11q, with LOH of the 9p being found in a third of cases, making it the most frequent chromosomal lesion described at the time.…”