Silent polymorphisms within the coding region of human sodium/hydrogen exchanger isoform-1 cDNA in peripheral blood mononuclear cells of leukemia patients: A comparison with healthy controls

We have examined the sequence of the cDNA encoding the sodium/hydrogen exch anger isoform 1 (NHE1), from 23 bases upstream of the start codon to 28 bas es downstream of the stop codon. Template was prepared from (1) peripheral blood mononuclear cells (PBMC) isolated from 10 healthy unrelated Caucasian volunteers; (2) PBMCs isolated from 6 leukemic patients (acute lymphoblast ic leukemia [ALL], n = 3; chronic lymphocytic leukemia [CLL], n = I; chroni c myelogenous leukemia [CML], n = 2); and (3) samples of 4 leukemic cell li nes (ALL: CEM, MOLT4; AML: KG1 alpha; CML: K562). NHE1 cDNA in normal PBMCs showed silent polymorphism of nucleotides 112 (N1: T, frequency 0.70; C, f requency 0.30; prevalence of heterozygosity 0.42); 2248 (N2: G, frequency 0 .90; A, frequency 0.10; heterozygosity 0.18); and 2493 (N3: G, frequency 0. 90; A, frequency 0.10; heterozygosity 0.18). Deduced primary structure of N HE1 protein in all normal volunteers was identical to that previously publi shed for NHE1 from renal and cardiac tissue. Similar to normal PBMCs, NHE1 cDNA from leukemic cells showed polymorphism of nucleotides NZ, N2, and N3, but failed to demonstrate leukemia-specific sequence differences. We concl ude that the coding region of NHE1 cDNA shows a greater level of polymorphi sm than is currently recognized, but that sequence mutation of NHE1 is not a key event in the pathogenesis of leukemia. (C) 2000 Elsevier Science Inc. All rights reserved.