title: Expression of T-lineage-affiliated transcripts and TCR rearrangements in acute promyelocytic leukemia: implications for the cellular target of t(15;17).
abstract: 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 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.
authors.affiliation: Department of Hematology, Université Paris-Descartes, Faculté de Médecine, and Institut National de la Santé et de la Recherche Médicale (INSERM) EMI0210, Assistance Publique-Hôpitaux de Paris (AP-HP) Necker-Enfants Malades, Paris, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Chapiro
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.forename: Vahid
authors.initials: V
authors.lastname: Asnafi
authors.forename: Corinne
authors.initials: C
authors.lastname: Millien
authors.forename: Frederic
authors.initials: F
authors.lastname: Davi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nugent
authors.forename: Kheira
authors.initials: K
authors.lastname: Beldjord
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: David
authors.initials: D
authors.lastname: Grimwade
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Macintyre
mesh_terms: D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D015331:Cohort Studies; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D038041:Lymphopoiesis / Q000235:genetics; D012333:RNA, Messenger; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D012333:RNA, Messenger; D014157:Transcription Factors