Identification of a novel, non-coding mRNA for the putative SHP-1 tumor suppressor gene

SHP-1 protein tyrosine phosphatase is a negative regulator for lymphocyte growth that has been postulated to function as a tumor suppressor. In primary human hematopoietic cells, only one mRNA transcript that encodes for a protein of 68 kDa has been described. Therefore, when two cell lines were identified that lacked SHP-1 protein, it was presumed that these cells lacked this transcript. However, further examination of these and other T cell lines using RT-PCR identified two additional SHP-1 transcripts. One was isolated from the Jurkat leukemia cell line and has a 130 nucleotide deletion that results in a truncated mRNA predicted to encode for a 7 kDa protein containing a partial aminoterminal SH2 domain. The second transcript, found in both normal and malignant cells, contains the entire unspliced first intron. This results in a frame shift and the formation of a non-coding mRNA species. This non-coding mRNA was the only transcript detected in the lymphoma-derived HUT 78 and leukemia-derived KIT 225 cells in which the SHP-1 protein was undetectable. This result supports a role for SHP-1 as a tumor suppressor in these cells. Although the mechanism is currently unknown, the lack of appropriate splicing out of the first intron of the SHP-1 gene during transcription may represent a novel mechanism involved in lymphomagenesis and may occur in different genes and explain other malignancies.