Expression of T-lineage-affiliated transcripts and TCR rearrangements in acute promyelocytic leukemia: implications for the cellular target of t(15;17)

Acute promyelocytic leukemia (APL) is the most differentiated form of acute myeloid leukemia (AML) and has generally been considered to result from transformation of a committed myeloid progenitor. Paradoxically, APL has long been known to express the T-cell lymphoid marker, CD2. We searched for other parameters indicative of T-cell lymphoid specification in a cohort of 36 APL cases, revealing a frequent but asynchronous T-cell lymphoid program most marked in the hypogranular variant (M3v) subtype, with expression of PTCRA, sterile TCRA, and TCRG transcripts and TCRG rearrangement in association with sporadic cytoplasmic expression of CD3 or TdT proteins. Gene-expression profiling identified differentially expressed transcription factors that have been implicated in lymphopoiesis. These data carry implications for the hematopoletic progenitor targeted by the PML-RARA oncoprotein in APL and are suggestive of a different cellular origin for classic hypergranular (M3) and variant forms of the disease. They are also consistent with the existence and subsequent transformation of progenitor populations with lymphoid/ myeloid potential.