REFINED CHROMOSOMAL LOCALIZATION OF THE HUMAN THROMBOPOIETIN GENE TO 3Q27-Q28 AND EXCLUSION AS THE RESPONSIBLE GENE FOR THROMBOCYTOSIS IN PATIENTS WITH REARRANGEMENTS OF 3Q21 AND 3Q26

Thrombocytosis is a characteristic clinical feature in patients with m yelocytic malignancies and chromosomal rearrangements of 3q21 and 3q26 , sometimes called the '3q21q26 syndrome'. The function of thrombopoie tin (TPO) in megakaryocytopoiesis and thrombopoiesis as well as its ch romosomal location, marked TPO as a candidate gene for malignancies wi th 3q rearrangements combined with dysmegakaryopoiesis. In this study 12 cases with inv(3)(q21q26) or t(3;3)(q21;q26) were analyzed by means of PFGE, but no rearrangements near the TPO locus were detectable. Si x YACs containing the TPO locus were isolated and characterized. By du al color in situ hybridization using a YAC from 3q26 containing the EV I1 gene and a YAC from the TPO locus, the localization of the human TP O gene could be refined to 3q27-q28 about 15-20 Mbp telomeric to the 3 q26 breakpoints occurring in myeloid malignancies. TPO levels were ana lyzed in the serum of three patients and were found to be in the norma l range. These results confirm the findings of two previous studies th at thrombopoietin expression is not the main cause of thrombocytosis i n the 3q21q26 syndrome.