CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCRgammadelta lineage.
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 alphabeta (TCRalphabeta) lineage T-ALLs, as defined by expression of TCRalphabeta, cytoplasmic TCRbeta, or TCRbetaVDJ rearrangement in immature cytoplasmic TCRbeta- cases, compared with 19% of TCRgammadelta 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 TCRgammadelta but not TCRalphabeta T-ALLs and in their TCRgamma and TCRdelta configurations, altogether suggesting that CALM-AF10+ immature delta/gammaT-ALLs are TCRgammadelta 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 TCRgammadelta 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+TCRgammadelta 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 TCRdelta rearrangements, suggesting that they may also be related to the TCRgammadelta 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 TCRgammadelta lineage.
Asnafi
Vahid
V
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, France.
Radford-Weiss
Isabelle
I
Dastugue
Nicole
N
Bayle
Chantal
C
Leboeuf
Daniel
D
Charrin
Christiane
C
Garand
Richard
R
Lafage-Pochitaloff
Marina
M
Delabesse
Eric
E
Buzyn
Agnes
A
Troussard
Xavier
X
Macintyre
Elizabeth
E
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000293:Adolescent; D000328:Adult; D019070:Cell Lineage / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002879:Chromosomes, Human, Pair 10; D002880:Chromosomes, Human, Pair 11; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics*; D011379:Prognosis; D017434:Protein Structure, Tertiary; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015996:Survival Rate; D014178:Translocation, Genetic
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C114359:AF10-CALM fusion protein, human; D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm; D016692:Receptors, Antigen, T-Cell, gamma-delta