A GENE ON CHROMOSOME XQ28 ASSOCIATED WITH T-CELL PROLYMPHOCYTIC LEUKEMIA IN 2 PATIENTS WITH ATAXIA-TELANGIECTASIA

A t(X;14)(q28;q11) translocation was present for many years in T cells in two patients with ataxia telangiectasia (A-T), who subsequently de veloped T-prolymphocytic leukemia. We describe here the relationship b etween the translocation break points in these patients with respect t o two recently described genes, c6.1A and c6.1B, on Xq28 which are tra nscribed in opposite directions from the same CpG island. In our first patient, the Xq28 breakpoint disrupts the c6.1A gene which is consequ ently transcribed as a fusion mRNA with the TCR Ca chain gene. In the second case, the Xq28 breakpoint lies within the adjacent gene c6.1B, and c6.1A is not transcribed. We show that the c6.1B gene is transcrib ed in both of our patients. c6.1B may be important in the initial clon al proliferation of T lymphocytes which commonly precedes transformati on to T-PLL in ataxia telangiectasia patients. The same gene may also be involved in the development of T-PLL in the non-A-T population.