Phenotypic conversion of acute leukaemia from T-lymphoblastic to myeloblastic induced by therapy with 2'-deoxycoformycin.
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.
D058892:Adenosine Deaminase Inhibitors; D002648:Child; D003070:Coformycin / Q000009:adverse effects* / Q000031:analogs & derivatives; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced*; D008297:Male; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin; D012263:Ribonucleosides / Q000009:adverse effects*; D013601:T-Lymphocytes
D058892:Adenosine Deaminase Inhibitors; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D009700:Nucleoside Deaminases