Elsevier

Human Pathology

Volume 44, Issue 10, October 2013, Pages 2365-2369
Human Pathology

Case study
A novel 5-way translocation t(9;11;13;19;22) in a case of chronic-phase chronic myeloid leukemia

https://doi.org/10.1016/j.humpath.2013.02.021Get rights and content

Summary

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder that occurs because of t(9;22)(q34;q11) translocations. Complex translocations have been reported in CML. We report a novel 5-way translocation 46,XY,t(9;11;13;19;22)(9q34.12;11p11.12;13q21.31;19q13.12;22q11.21) using GTG banding, fluorescence in situ hybridization, and spectral karyotyping in a case of chronic-phase CML. Molecular analysis revealed the presence of 2 types of transcripts (b3a2, b2a2). The patient was responding to the imatinib treatment. However, the patient needs to be carefully monitored at various intervals.

Introduction

Chromosomal translocations are common in cancer cells, and some translocations produce oncogenes that are responsible for malignant transformation. Complex chromosomal translocations are defined as structural chromosomal rearrangements and exchanges of genetic material between 2 or more chromosomes. Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder. It occurs because of translocations between chromosomes 9 and 22, designated as t(9;22)(q34;q11), forming a malignant BCR/ABL fusion gene on a novel chromosome called Philadelphia chromosome (Ph). The classical pattern of the Ph chromosome occurs in 95% of CML cases; the remaining cases show additional chromosomes or complex translocations. Here, we report a novel case of CML in chronic phase with complex Ph translocation involving the 5 chromosomes 9, 22, 19, 11, and 13.

Section snippets

Case history

A 29-year-old man with no significant medical history was referred for cytogenetic investigation because of leukocytosis. No significant unusual clinical or morphologic feature was observed in the patient. A complete hemogram showed a hemoglobin level of 7.4 g/dL with a mean corpuscular volume of 88, platelet count of 659 erythrocyte sedimentation rate, and white blood cell count of 223 800/μL with a differential count of 35% polymorphs, 7% basophils, 6% blasts, 5% promyelocytes, 24%

Conventional cytogenetics

Conventional cytogenetic analysis was performed on the bone marrow sample of the patient according to the standard procedure. The chromosomal preparations were subjected to GTG banding. Thirty well-spread and banded metaphases were analyzed and karyotyped according to the 2009 International System for Human Cytogenetic Nomenclature [1].

Molecular cytogenetics

Fluorescence in situ hybridization (FISH) was done using a BCR/ABL probe (Vysis, Abbott Molecular Inc., Des Plaines, IL), and whole chromosome paint probes for

Conventional cytogenetics

Conventional cytogenetics on the bone marrow sample gave the impression of a complex Ph translocation involving the 5 chromosomes 9, 22, 11, 19, and 13 (Fig. 1A and B). However, the translocation of the 3′ part of the BCR gene was untraceable. To get a clear picture of the translocations, molecular cytogenetic methods like FISH and SKY were used.

Molecular cytogenetics

FISH using a dual-color, dual-fusion BCR/ABL probe revealed BCR/ABL single fusion in 95% of metaphase and interphase cells. The signal pattern observed

Discussion

Additional chromosomal abnormalities are observed at diagnosis in less than 10% of the cases of CML-chronic phase (CP). Occurrence of additional chromosomal abnormalities in Ph-positive cells can be a primary event or a secondary event. The complex chromosomal abnormalities also have been reported in CML cases. However, 5-way translocation is a rare occurrence. In our case, the chromosomes 9, 11, 13, 19, and 22 were involved in complex translocation including the Ph chromosome. The 5-way

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