Analysis of cellular models of clonal evolution reveals co-evolution of imatinib and HSP90 inhibitor resistances.

Treatment relapse due to clonal evolution was shown to be an independent factor for poor prognosis in advanced stages of chronic myeloid leukemia. Overcoming secondary resistance arising due to clonal evolution is still an unmet need and lack of adequate pre-clinical models hampers the identification of underlying mechanisms and testing of alternate treatment strategies. The current study thus aimed to create cellular models to study molecular mechanisms underlying clonal evolution and identify strategies to overcome the secondary drug resistance.

Rare Disorder of Sexual Differentiation with a Mosaic 46,XX/47,XXY in a Klinefelter Syndrome Individual.

Background: Klinefelter syndrome (KS) mosaicism 46,XX/47,XXY is an extremely rare disorder of sex development characterized by the presence of both ovarian and testicular tissues in the same individual. Both elements can be present in the same gonad (ovotestis) or separately in the same individual or as a unilateral ovotestis and the other side with testis or ovary. A mosaic with 46,XY would present with problems related to male infertility and in general, testicular insufficiency, but with a 46,XX mosaic, it is a completely rare presentation.