Phenotypic conversion of acute leukaemia from T‐lymphoblastic to myeloblastic induced by therapy with 2′‐deoxycoformycin

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Abstract
Summary.: A 6‐year‐old boy with T‐cell acute lymphoblastic leukaemia (ALL) in relapse was treated with the adenosine deaminase inhibitor, 2′‐deoxycoformycin (DCF). Remarkably, his residual leukaemia underwent an abrupt phenotypic shift, coincident with a massive anti‐leukaemic effect of DCF. Both at diagnosis and prior to therapy with DCF, blast cells had typical lymphoblastic morphology and T‐cell characteristics (terminal transferase +, T‐antigen +, Ia –, cALLa –, myeloperoxidase –, and high in adenosine deaminase content). After four courses of DCF by constant infusion, the blast cells were myeloid in appearance and reactivity to a variety of tests (terminal transferase –, myeloperoxidase +, Sudan black B +, esterase +, My‐1 +). We hypothesize that DCF therapy created a selection pressure, blocking pathways of T‐cell differentiation and proliferation, permitting the emergence of a newly dominant myeloid subclone of a multipotential leukaemic cell progenitor with the innate capacity for both T‐lymphocytic and myeloid differentiation.