DNA Genotypic Conservation During Phenotypic Switch from T-cell Acute Lymphoblastic Leukaemia to Acute Myeloblastic Leukaemia

Abstract

This communication reports a case of T-cell acute lymphoblastic leukaemia (T-ALL) which, after treatment and remission induction, relapsed 17 months after apparent disease-free remission as acute myeloblastic leukaemia (AML). Extensive immunophenotypic, analysis an initial presentation revealed a typical T-ALL phenotype (HLA-Dr^-, TdT⁺, CD2⁺, CD3⁺, CD4^-, CD5⁺, CD7⁺, CD8^-, CD19^-, CD13/33^-) that was unusual in that the majority of blasts expressed membrane TCR γδ chains but not TCR αβ chains. Similarly, the morphological (Auer rods +), cytochemical (MPO⁺ and SBB⁺) and phenotypic characteristics at relapse were unequivocably consistent with a diagnosis of AML. In contrast to previous case studies of “phenotypic switch” or “metachronous bilineal leukaernia”, Southern blot analysiis of TCR and Ig gene rearrangements at presentation and relapse were able, because of an unusual genotypic pattern (TCR β +, TCR γ +, TCR δ + and J_H), to confirm the common clonal origin of the two leukaemias. It is suggested that the transition from T-ALL to AML may not be a “random” phenomenon but may rather reflect subclonal domination by mycloid blasts with relative drug resistance (i.e. synchronous bilineal differentiation with an undetectable myeloid component), or therapy-induced alterations in the balance of (myelosuppressive) factors.

Key Words:

• Bilineal leukaemia
• mixed-lineage leukaemia
• phenotypic switch
• gene rearrangements