Pattern of expression of five alternative transcripts of the lck gene in different hematopoietic malignancies: correlation of the level of lck messenger RNA I B with the immature phenotype of the malignancy.

Abstrad The Ick gene encodes a tyrosine protein kinase of the src family which is highly expressed in T-lymphocytes. Two widely separated promoters govern expression of the !ck gene. We report in this study that alternative splicing between cryptic donor and acceptor sites in the 5’ untranslated region of the transcripts initiated at the type I promoter give rise to three different type I !ck mRNAs, I A, I B, and I C. Altogether with the types II A and II B reported previously, the !ck transcription is thus charaderized by five alternative transcripts. We further used the complementary DNA-polymerase chain readion assay to describe the pattern of expression of these five !ck transcripts in different hematopoietic cell lines and in blood or bone marrow samples from healthy donors and leukemic patients. We report that the transcript II A is by far the major transcript present both in human samples and in T-cell lines. The low !ck expression in B-cell lines is charaderized by the quite exclusive presence of the transcript I B. We show that hematopoietic diseases charaderized by the presence of immature cells [acute myeloid leukemia (AML-O and AML-1) and T- and B-cell acute lymphoid leukemia] exhibit a marked increase of the transcript I B. No significant difference from the normal pattern is observed in AML according to the differentiation stage (AML-2 to AML-5). A normal pattern of !ck expression is restored in AML-O and AML-1 patients at complete remission.