Alternative splicing in wild-type AF10 and CALM cDNAs and in AF10-CALM and CALM-AF10 fusion cDNAs produced by the t(10;11)(p13-14;q14-q21) suggests a potential role for truncated AF10 polypeptides.
The t(10;11)(p13;q14-21) is a non-random translocation that occurs primarily in T cell acute lymphoblastic leukemias (T-ALL), but has also been observed in leukemias and lymphomas of diverse lineages. In U937, a cell line established from a diffuse histiocytic lymphoma, a t(10;11)(p13;q14-21) fuses AF10 to CALM. AF10 is also fused to MLL by a translocation that appears quite similar at the cytogenetic level, the t(10;11)(p12;q23). Fluorescence in situ hybridization studies have demonstrated that AF10 and CALM are also involved in other hematological malignancies containing t(10;11)(p13;q21), but no data are available concerning the molecular details of AF10-CALM fusion in primary leukemias. Using RT-PCR, we amplified multiple different isoforms of AF10-CALM and CALM-AF10 fusion cDNAs from a primary T cell ALL containing a t(10;11)(p13-14;q14-21). These cDNAs arose via alternative splicing of exons from both AF10 and CALM, which we demonstrated can also occur in the native genes. We identified at least two novel AF10 exons that can be included in wild-type and fusion cDNAs. The majority of the AF10 and AF10-CALM cDNA isoforms that we identified are predicted to encode for truncated AF10 polypeptides, raising the possibility that these might have important cellular functions in normal and malignant cells, perhaps by acting as dominant negative inhibitors of full-length AF10 or related proteins.
Silliman
C C
CC
Department of Pediatrics, University of Colorado School of Medicine, The Children's Hospital, Denver, USA.
McGavran
L
L
Wei
Q
Q
Miller
L A
LA
Li
S
S
Hunger
S P
SP
D033942:Adaptor Proteins, Vesicular Transport; D000293:Adolescent; D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D005260:Female; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics*; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
C114359:AF10-CALM fusion protein, human; D033942:Adaptor Proteins, Vesicular Transport; D018076:DNA, Complementary; D004273:DNA, Neoplasm; C092513:MLLT10 protein, human; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins; D015514:Oncogene Proteins, Fusion; C439003:PICALM protein, human; D010750:Phosphoproteins; D014157:Transcription Factors