Rearrangement and amplification of c-abl sequences in the human chronic myelogenous leukemia cell line K-562.

Abstract

Structural rearrangements of specific cellular sequences (c-onc genes) homologous to acute transforming retrovirus oncogenes (v-onc genes) have been recently described in various malignancies. Here we show that human cellular sequences (c-abl) homologous to the transforming sequences of the mouse Abelson leukemia virus (v-abl) are amplified some 4-to 8-fold in K-562, a Philadelphia chromosome-positive cell line derived from a patient with chronic myelogenous leukemia in blast crisis. Restriction analysis of K-562 and other human DNA samples reveals a significant rearrangement of the c-abl sequences in this cell line.In addition, investigation of v-abl-related cytoplasmic RNA reveals relatively high levels of these sequences in K-562 compared to other normal and leukemia cells. We have also observed that A light chain constant region immunoglobulin genes are amplified in K-562, whereas K light chain sequences exhibit no amplification. These results are discussed within the context of the possi-

BCR-ABL-transduced human cord blood cells produce abnormal populations in immunodeficient mice

“…The cells in this clone contained one copy of the BCR-ABL gene and were highly skewed towards an erythroid differentiation program. The level and degree of phosphorylation exhibited by the p210 BCR-ABL expressed in these cells was equivalent to that seen in K562 cells, a cell line developed from a CML patient with blast phase disease that contains multiple copies of the BCR-ABL oncogene 21,22 and also displays evidence of erythroid differentiation. 23 Thus, some of the features obtained in this in vivo xenograft model are more reminiscent of blast phase CML where higher levels of BCR-ABL expression are typically seen 24,25 and perturbations of differentiation are usually more exaggerated.…”

Amplification of the ABL gene in T-cell acute lymphoblastic leukemia

“…3,5 Although amplification of the BCR/ABL fusion gene has been described in cases of chronic myeloid leukemia (CML) treated with imatinib mesylate, seen both as HSRs 6 and dmins, 7 amplification of ABL alone is rare. A six-fold and a 15-fold amplification of the gene have been described in the CML-derived cell line, K562, 8 and in a patient with CML in lymphoid blast crisis, respectively. 9 The only other FISH report of amplification involving ABL was in three cases of secondary AML.…”

“…K562 is known to have an approximately six-fold amplification of ABL. 8 In our patient sample (3183), ABL was amplified at least five-fold in comparison with K562, taking into consideration that only 67% of the cells within the bone marrow sample showed evidence of amplification. Examination of the ethidium bromide gel confirmed that the increased signal intensity in K562 and patient 3183 was not a loading artefact.…”

Oncogenes and human leukemias

“…In the HL-60 myeloid cell line and in fresh leukemia cells from patients, c-myc was reportedly amplified [21,22]; it was also amplified in one case of CML during progression from chronic to acute phase [23] and in [24]. Several authors have reported amplification of c-abl in K562, an erythroleukemia cell line containing the t(9;22) translocation typical of CML [25]. In K562, the amplification unit of the translocated c-abl involves the Ig lambda light-chain constant region (Ch), implying that the amplification occurred subsequent to translocation of c-abl from chromosomes 9 to 22, the map site of Ch [26].…”