Poulsom, R.; Campbell, V.; Jeffery, R.; Hunt, T.; Alison, M.R.; Quaglia, A.; Dhillon, P.A.; Wright, N.A.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA56
Academic Journal
Introduction: Bone marrow cells can cross lineage boundaries and transdifferentiate into a wide variety of cell types. Such plasticity is seen after transplantation, if histocompatibility or genetic markers are used. Chronic granulocytic (myeloid) leukaemia (CML) is a neoplastic proliferation of an early haematopoietic stem cell that can differentiate into most haematopoietic lineages; ∼95% of CML cases have a reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22); the abnormal chromosome 22 is known as the Philadelphia (Ph) chromosome. We sought to discover if Ph-positive bone marrow cells could transdifferentiate into hepatocytes in vivo. Methods: We examined liver biopsies of 4 cases of CML (cytogenetics confirmed that 3 cases were Ph-positive and one had a different translocation) and a biopsy from an unrelated pathological case. The presence of normal or fused genes was visualised by fluorescence and confocal microscopy using directly-labelled DNA Fluorescence In Situ Hybridisation (FISH) probes. One thousand morphologically identified hepatocytes were examined from each case. Results: In the two Ph-negative cases most hepatocytes had two separate orange signals and two separate green signals; no fusion of orange and green signals (producing an overlapping yellow signal) indicative of the BCR-ABL fusion gene was seen. In contrast, in the liver biopsies of the 3 Ph-positive cases of CML, the hybrid fusion gene was observed in 0.6, 1.0 and 1.3% of hepatocyte nuclei. Ph-positive hepatocytes were not morphologically abnormal. Conclusions: Our study supports the concept that bone marrow cells transdifferentiate into hepatocytes in the human liver without the trauma and associated stresses of transplantation. The presence of the Philadelphia chromosome appears not to impede this lineage switch.


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