HLA-DR-associated invariant chain is highly expressed in chronic lymphocytic leukemia

Abstract

Total RNA extracted from peripheral blood lymphocytes of a patient with B-cell chronic lymphocytic leukemia (CLL) and the poly (A+) RNA was purified. A cDNA library was constructed and approximately 4,000 clones were screened in order to identify genes preferentially expressed in CLL. A relatively low repetition frequency characterizes the majority of the abundant mRNA species present in CLL lymphocytes. One clone, corresponding to the mRNA encoding the HLA-DR-associated invariant chain, was selected and its expression was examined in different leukemic cell populations and in normal tissues. DNA-RNA hybridization studies showed that the invariant chain mRNA (In-mRNA) is detectable in RNA preparations from human blood cells and their precursors, whereas no In-mRNA is found in several other tissues examined. Among various normal and leukemic leukocyte populations, the highest levels of In- mRNA are found in CLL. Therefore, a role of In-chain mRNA as a marker of CLL is proposed. Our data support a relationship between high levels of invariant chain mRNA and the out of cycle condition of CLL peripheral blood lymphocytes.

Structure of the human gene encoding the invariant γ-chain of class II histocompatibility antigens

“…Invariant y-chain mRNA is made in human blood cells and their precursors but has not been detected in a variety of other human tissues (10), such as among various leukemic leukocyte populations the highest levels of y-chain mRNA were found in patients with CLL. These data support a relationship between high levels of y-chain mRNA and the nonproliferating condition of the cell (10,37,38).…”

“…In a previous study to identify the cDNAs that are preferentially expressed in human leukemias, we selected a clone (p7-2D-1) that was more highly expressed in chronic lymphocytic leukemia (CLL) than in several other tissues (9). Subsequent experiments have shown that this gene is expressed in human blood cells and their precursors but not in placenta, liver, kidney, pancreas, gut, or muscle (10). In normal cells the highest expression is found in resting peripheral blood B-lymphocytes. In this communication we present the nucleotide sequence of the structural gene with its 5' and 3' flanking regions.…”

Regulation of CLL survival by hypoxia‐inducible factor and its target genes

“…In addition, anti‐MIF Ig therapy was shown to suppress tumor growth [42]. CD74 overexpression was observed in various cancers [43–48] including CLL [49,50]. CD74 expression in solid tumors has been suggested to serve as a prognostic factor, with higher relative expression of CD74 behaving as a marker of disease progression [51].…”