br Discussion Bone marrow fibrosis
Discussion Bone marrow fibrosis is known to be associated with hematolymphoid malignancies such as acute leukemia, Hodgkin and non-Hodgkin lymphoma. Among the acute leukemias, marrow fibrosis is most often seen with acute megakaryoblastic leukemia. It is an uncommon finding in APL and till date only handful of case reports are seen in literature, however its presence does not seem to alter the prognosis of APL [4,7]. Hatake et al. demonstrated bone marrow fibrosis following therapy with tretinoin and also proved that the fibrosis is reversible after stopping tretinoin and chemotherapy . However there is no reports so far mentioned in literature regarding marrow fibrosis post ATO therapy, hence our case would be the first of its kind with this unique finding. In APL ATO has dose dependant effect on promyelocytes inducing preferential apoptosis at high concentration (0.5–2μmol/L), inducing partial differentiation at low concentration (0.1–0.5μmol/L) and causing modulation and degradation of PML-RARα protein at a dose of 0.1–0.2μmol/L . Mori et al. suggested a possible role of transforming growth factor beta (1) (TGF-β1) in causing the fibrosis in APL as they ptio have noticed the overexpression of TGF-β1 by RT-PCR . A similar mechanism is possible with ATO in inducing bone marrow fibrosis as brought out by Chu et al. who had established the role of ATO-induced TGF-β1secretion from cardiac fibroblasts which resulted in myocardial fibrosis . In the same line Szymańska-Chabowska et al. demonstrated the role of arsenic in liver fibrosis leading to chronic hepatic failure . Hence it can be said with reasonable confidence that, as ATO is capable of inducing fibrosis in heart and liver, it is possible for ATO to induce bone marrow fibrosis as well even though it is not mentioned in literature so far. Whether this ATO induced fibrosis in unique to the cytogenetic abnormality this patient has, needs to be explored. Also the outcome of this marrow fibrosis needs to be ascertained from further follow up of this patient. As RT-PCR for PML-RARα will not help in this case to assess the molecular remission, the patient needs to be followed up with conventional cytogenetics or FISH analysis for molecular remission status. This case had so many unusual features such as a long duration of illness, uncommon morphological findings, rare cytogenetic abnormality and ATO induced bone marrow fibrosis. Hence the case is reported for this constellation of unique features.
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