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Prepublished online as a Blood First Edition Paper on April 3, 2003; DOI 10.1182/blood-2002-09-2913.

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2002-09-2913v1
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Blood, 1 August 2003, Vol. 102, No. 3, pp. 1000-1006

NEOPLASIA

CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCR{gamma}{delta} lineage

Vahid Asnafi, Isabelle Radford-Weiss, Nicole Dastugue, Chantal Bayle, Daniel Leboeuf, Christiane Charrin, Richard Garand, Marina Lafage-Pochitaloff, Eric Delabesse, Agnès Buzyn, Xavier Troussard, and Elizabeth Macintyre

From the Laboratoire d'Hematologie, Service d'Histologie, Embryologie, et de Cytogenetic, Service d'Hematologie Clinique, Centre Hospitalier Universitaire (CHU) Necker Enfants Malades and University Paris V; Laboratoire d'Hematologie et Genetique des Hemopathies, CHU Purpan, Toulouse; Laboratoire d'Hematologie, Institut Gustave Roussy, Villejuif; Laboratoire d'Hematologie, CHU Edouard Herriot, Lyon; Institut de Biologie des Hopitaux, CHU Nantes; Departement de Biologie, Unite de Genetique Hematologique, Institut Paoli Calmette, Marseille; and Laboratoire d'Hematologie, CHU Caen, France

The t(10;11)(p13-14;q14-21) associated with CALM-AF10 is considered to be rare and associated with a variety of acute lymphoid and myeloid leukemias. Twelve (9%) of 131 unselected T-cell acute lymphoid leukemias (T-ALLs) expressed CALM-AF10 by reverse transcription–polymerase chain reaction or fluorescence in situ hybridization (or both), including 8% of children and 10% of adults, of whom only half demonstrated a t(10;11) by classical cytogenetics. CALM-AF10 was not found in T-cell–receptor {alpha}{beta} (TCR{alpha}{beta}) lineage T-ALLs, as defined by expression of TCR{alpha}{beta}, cytoplasmic TCR{beta}, or TCR{beta}VDJ rearrangement in immature cytoplasmic TCR{beta}- cases, compared with 19% of TCR{gamma}{delta} T-ALLs and 33% of immature {delta}/{gamma} T-ALLs. The latter differed from their CALM-AF10- immature counterparts by a CD5+/CD2-phenotype, as found in TCR{gamma}{delta} but not TCR{alpha}{beta} T-ALLs and in their TCR{gamma} and TCR{delta} configurations, altogether suggesting that CALM-AF10+ immature {delta}/{gamma}T-ALLs are TCR{gamma}{delta} precursors and that, within T-ALL, CALM-AF10 is specific for this lineage. Nine of 12 immature CALM-AF10 T-ALLs demonstrated 3' fusion transcripts, whereas 6 of 7 TCR{gamma}{delta} T-ALLs demonstrated 5' fusion transcripts. The latter retain the AF10 extended LAP/PHD domain necessary for homo-oligomerization. All 8 patients with CALM-AF10+TCR{gamma}{delta} T-ALLs are alive, compared with only 3 of 12 with immature CALM-AF10+ T-ALLs. Six CALM-AF10+ non-T acute leukemias all expressed CD7 and demonstrated T-restricted TCR{delta} rearrangements, suggesting that they may also be related to the TCR{gamma}{delta} lineage. CALM-AF10 is therefore the most common fusion protein in T-ALL. It requires molecular and immunophenotypic characterization for appropriate prognostic evaluation and should be included in diagnostic screening panels of T-ALL and immature acute leukemias. Analysis of immature CALM-AF10+ leukemias will also facilitate analysis of the early stages of development of the TCR{gamma}{delta} lineage.


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