Elsevier

Leukemia Research

Volume 22, Issue 9, September 1998, Pages 793-796
Leukemia Research

No parental origin bias for the rearranged chromosomes in myeloid leukemias associated with t(9;22), t(8;21) and t(15;17)

https://doi.org/10.1016/S0145-2126(98)00069-1Get rights and content

Abstract

We investigated parental origin of rearranged chromosomes 9 and 22 (9q+ and 22q−) in five patients with Ph-positive chronic myeloid leukemia (CML) using the C-banding and silver-staining methods of nucleolus organizer regions, respectively; of rearranged chromosome 21 (21q+) in seven patients with t(8;21)-positive acute myeloid leukemia (AML); and of rearranged chromosome 15 (15q+) in six patients with t(15;17)-positive AML. It was found that these rearranged chromosomes can be of either paternal or maternal origin. Although the number of patients examined was small, these results indicate that the genes rearranged as a result of these chromosome translocations (ABL, BCR, AML-1 and PML) are not genomically imprinted.

Introduction

A reciprocal translocation between chromosomes 9 and 22, t(9;22) (q34;q11), is characteristic of chronic myeloid leukemia (CML). Based on heterochromatin polymorphisms in these chromosomes, Haas et al. [1]reported that the origins of the rearranged chromosomes 9 and 22 (9q+and 22q−) in CML patients were exclusively paternal and maternal, respectively. This parent of origin bias would be an example of genomic imprinting. This result led to the hypothesis that the genes disrupted and rearranged by the translocation, i.e. ABL and BCR, were themselves imprinted. However, several later reports, using molecular methods, have shown that the ABL and BCR genes are not imprinted 2, 3, 4, 5, 6. In this study, we tried to reproduce the Haas et al. investigation with the same method employed by that original group [1]. Furthermore, we cytogenetically investigated the origin of rearranged chromosome 21 (21q+) in acute myeloid leukemia (AML) with t(8;21)(q22;q22) and of rearranged chromosome 15 (15q+) in AML with t(15;17)(q22;q21), since chromosomes 15 and 21 are acrocentric and their heterochromatin polymorphisms are distinguishable by the silver-staining patterns of nucleolus-organizing regions (NORs) on the short arms.

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Materials and methods

We examined five CML patients with t(9;22), seven AML patients with t(8;21) and six AML patients with t(15;17). Blood samples were obtained from all parents with informed consent. The cell samples for cytogenetic studies were obtained from bone marrow (BM) of the patients and from peripheral blood (PB) of the parents. Whenever possible, PB samples from the patients were also examined to confirm that the heterochromatin polymorphism patterns between the PB and BM cells were identical. BM samples

Results

The parental origins of the rearranged chromosomes were found by C-banding or Ag-NOR-staining method in 10 of the 18 patients examined (Table 1). Among the five patients with CML, one had paternal 9q+ and maternal 22q−, one maternal 9q+ and paternal 22q− and one undetermined 9q+ and maternal 22q−. The parental origins of the rearranged chromosomes in patient 2 contradict the results of Haas et al. [1]. The partial karyotypes of the patient and her parents are shown in Fig. 1. Among the seven

Discussion

In this study, we attempted to reproduce the results of Haas et al. using the same method that they employed [1]and found that some CML patients may have maternal 9q+ and paternal 22q− chromosomes.

Haas et al. showed a marked parent of origin bias in the chromosomes involved in the t(9;22) by using heterochromatin polymorphisms [1]. In 1994, however, Riggins et al. [2]and Fioretos et al. [3]reported that the normal BCR gene is expressed from both alleles by using a polymorphic CGG-repeat and a

Acknowledgements

The authors thank Professor Yoshiro Tsuji and Dr Masahiko Nakayama (Department of Pediatrics, Nagasaki University School of Medicine) for providing clinical data of some patients. This study was supported by Grant-in-Aid for Exploratory Research from the Ministry of Education, Japan.

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