Chronic Myeloproiferative Disorders (CMPDs) are a spectrum of haematological malignancies of which the molecular pathogenesis remains unknown. Chronic Myeloid Leukaemia (CML) being the only disorder with a recognisable pathogenomic abnormality, the Ph chromosome. Recent published data has supported the role of tyrosine kinases in the disease pathogenesis, in particular the role of a cytoplasmic tyrosine kinase JAK2. It has been shown that >80% of Polycythaemia Vera (PV) patients and 30% of Essential Thrombocythaemia (ET) patients demonstrate a clonal and recurrent mutation V617F in the JH2 pseudo-kinase domain of JAK2 located on 9p24.1. Our array CGH investigations of cell lines, established from lymphoid and myeloid blast phase samples revealed a complex pattern of imbalances affecting the short arm of chromosome 9: on the background of 2–3-fold amplification, a loss of the 9p24.1 region, which harbours the JAK 2 sequences was repeatedly observed. FISH using BAC DNA probes from the 9p24.2 and 9p23 region was carried out to map the JAK2 gene and the flanking sequences. Results so far indicate the presence of both imbalances (amplifications & deletions) and rearrangements involving the JAK2 region in 5 cell lines. An on going FISH study of CMPD patients (CML, PV, ET and MF) with normal and abnormal karyotypes has revealed 9p24 imbalances in 18% (5 out of 28). The observation of JAK2 aberrations in a range of haematological malignancies demonstrates the potential importance of tyrosine kinases in the leukemogenesis. The pathegenomic significance of aberrations found in the region surrounding JAK2 has yet to be defined and our study demonstrates the importance of molecular cytogenetics as a tool in understanding the significance of JAK2 in CMPDs.

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