Expression of beta 1 integrin mRNAs in human leukemic blasts

Adhesion receptors from the very late activation (VLA) (beta 1) integrin subfamily play a role in the cooperation of hematopoietic progenitors with bone marrow stroma, and the disregulated expression of these molecules, as evaluated by immunophenotyping, has been implicated in the acquisition of the malignant phenotype by hematopoietic cells. In the present study, Northern hybridization was used to determine the pattern of expression of transcripts for VLA subunits in: (i) leukemic blasts obtained from the peripheral blood of ten patients with acute myelogenous leukemia (AML) of different FAB subclasses; (ii) the human leukemic cell lines KG-1, HL-60, K-562, HEL and U-937; and (iii) normal hematopoietic cells. Most of the AML blasts and the cultured leukemic cells expressed mRNAs for the beta 1 and alpha 5 subunits (the only exception among the cell lines was KG-1 cells) and these transcripts were also found in normal bone marrow progenitors, peripheral blood mononuclear cells (PBMNC), and peripheral blood monocytes. While the alpha 4 transcript was detected in all cultured cells but K-562, and in normal circulating monocytes, it occurred in blasts from only two AML patients and was weakly expressed in mature PBMNC. No specific pattern of expression of beta 1, alpha 5, and alpha 4 transcripts could be related to cell differentiation or maturation in the AML blasts and leukemic cell lines tested. None of the primary AML blasts or cultured cells showed mRNA messages for alpha 2, alpha 3 or alpha 6 chains of the beta 1 integrins. The results suggest that, in some cases of AML, the malignant phenotype of leukemic blasts may be associated with down-regulated transcription of the alpha 4 integrin subunit.