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

Submitted September 24, 2002
Accepted March 22, 2003
CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCR lineage
Vahid Asnafi, Isabelle Radford-Weiss, Nicole Dastugue, Chantal Bayle, Daniel Leboeuf, Christiane Charrin, Richard Garand, Marina Lafage-Pochitaloff, Eric Delabesse, Agnes Buzyn, Xavier Troussard, and Elizabeth Macintyre*
Laboratoire d'Hematologie, CHU Necker Enfants Malades and University Paris V, Paris, France
Service d'Histologie, Embryologie, et de Cytogenetic, CHU Necker Enfants Maladesand University Paris V, Paris, France
Laboratoire d'Hematologie et Genetique des Hemopathies, CHU Purpan, Toulouse, France
Laboratoire d'Hematologie, Institut Gustave Roussy, Villejuif, France
Laboratoire d'Hematologie, CHU Edouard Herriot, Lyon, France
Institut de Biologie des Hopitaux, CHU Nantes, Nantes, France
Departement de Biologie, Unite de Genetique Hematologique, Institut Paoli Calmette, Marseille, France
Service d'Hematologie Clinique, CHU Necker Enfants Malades, Paris, France
Laboratoire d'Hematologie, CHU Caen, Caen, France
* Corresponding author; email: elizabeth.macintyre{at}nck.ap-hop-paris.fr.
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-ALLs expressed CALM-AF10 by RT-PCR and/or FISH, including 8% of children and 10% of adults, of which only half demonstrated a t(10;11) by classical cytogenetics. CALM-AF10 was not found in TCR lineage T-ALLs, as defined by expression of TCR , cytTCR and/or TCR VDJ rearrangement in immature (IM) cytTCR - cases, compared to 19% of TCR T-ALLs and 33% of IM / T-ALLs. The latter differed from their CALM-AF10 negative immature counterparts by a CD5+/CD2- phenotype, as found in TCR but not TCR T-ALLs and in their TCR and TCR configurations, altogether suggesting that CALM-AF10+ IM / T-ALLs are TCR 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 6/7 TCR T-ALLs demonstrated 5' fusion transcripts. The latter retain the AF10 extended LAP/PHD domain necessary for homo-oligomerisation. All 8 CALM-AF10+ TCR T-ALLs are alive, compared to only 3/12 immature CALM-AF10+ T-ALLs. Six CALM-AF10+ non-T acute leukemias all expressed CD7 and demonstrated T restricted TCR rearrangements, suggesting that they may also be related to the TCR 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 AL. Analysis of immature CALM-AF10+ leukemias will also facilitate analysis of the early stages of TCR lineage development.

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