A MAPPING STUDY OF 13 GENES ON HUMAN-CHROMOSOME BANDS 4Q11-]Q25

A chromosome band 4q21 gene(MLLT2, formerly called AF-4/FEL) involved in a reciprocal translocation with chromosome band 11q23 in t(4;11) ac ute leukemia has been cloned. To provide better definition of gene ord er and relationships in this region where MLLT2 resides, we used pulse d field gel electrophoresis (PFGE) to investigate 13 genes (including MLLT2) with physical locations in bands 4q11-->q25. Somatic cell hybri ds derived from RS4;11, a leukemic cell line carrying the t(4;11)(q21; q23), were also used to localize genes in relation to MLLT2. Linkage o f the interleukin 8 (IL8), albumin (ALE), and platelet factor 4 (PF4) genes was confirmed by NotI, SalI and SacII digests. The maximum dista nce between PF4 and ALE is 210 kb and between ALE and IL8 is 420 kb. T he alcohol dehydrogenase, class I (ADH2, ADH3) gene cluster can be lin ked to the alcohol dehydrogenase, class III gene (ADH5) by SacII, NruI , and EagI digests. The maximum distance between them is 590 kb. Our s tudy indicated that ALE, a-fetoprotein (AFP), PF4, beta-thromboglobuli n (PPBP), GRO1 (encoding a cytokine also called melanoma growth-stimul atory activity), and IL8 genes can be physically linked. In this study the gamma-interferon induced protein 10 (INP10), bone morphogenetic p rotein 3 (BMP3), annexin III (ANX3), KIT, amphiregulin (AREG), immunog lobulin J polypeptide (IGJ), deoxycytidine kinase (DCK) and MLLT2 gene s were not linked to one another or to the above two groups of genes. Our analysis using somatic cell hybrids combined with previous reports demonstrated that the ADH gene cluster is telomeric to MLLT2 and KIT, ALB, AFP, PF4, beta TG, GRO1, IL8, ANX3, AREG and DCK are centromeric to MLLT2.