Submitted September 22, 2005
Accepted June 28, 2006
Expression of T-lineage affiliated transcripts and TCR rearrangements in acute promyelocytic leukemia: implications for the cellular target of the t(15;17)
Elise CHAPIRO, Eric DELABESSE, Vahid ASNAFI, Corinne MILLIEN, Frederic DAVI, Elizabeth NUGENT, Kheira BELDJORD, Torsten HAFERLACH, David GRIMWADE, and Elizabeth A MACINTYRE*
Department of Hematology, Universite Paris-Descartes, Faculte de Medecine, and INSERM EMI0210, AP-HP
Department of Hematology, AP-HP La Pitie-Salpetriere, Paris, FR
Department of Medical and Molecular Genetics, King's College London, UK
MLL Munich Leukemia Laboratory, Munich, GE
King's College London, UK
* Corresponding author; email: elizabeth.macintyre{at}nck.aphp.fr.
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 hematopoietic progenitor targeted by the PML-RARA oncoprotein in APL and are suggestive of a different cellular origin for classical 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.
