Ann Lab Med.  2015 Jan;35(1):128-131. 10.3343/alm.2015.35.1.128.

Submicroscopic Deletions of Immunoglobulin Heavy Chain Gene (IGH) in Precursor B Lymphoblastic Leukemia with IGH Rearrangements

• Huh J
• Mun YC
• Yoo ES
• Seong CM
• Chung WS

• KMID: 2363160
• DOI: http://doi.org/10.3343/alm.2015.35.1.128

Abstract

Translocations leading to fusions between the immunoglobulin heavy chain gene (IGH) and various partner genes have been reported in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, submicroscopic deletions within IGH in B-ALL have not been rigorously assessed. In this study, we investigated characteristics of IGH submicroscopic deletions, by FISH, in B-ALL with IGH rearrangements. FISH was performed by using commercially available IGH dual-color break-apart rearrangement probes (Abbott/Vysis, Downers Grove, IL, USA; Kreatech, Amsterdam, Netherlands). The study group included seven B-ALL patients with IGH rearrangements, observed by FISH. Among them, two exhibited deletion of the 5' variable region of IGH by FISH. The B-ALL in these two patients included two kinds of abnormal cells; one had an IGH rearrangement without any IGH submicroscopic deletion, while the other had an IGH submicroscopic deletion, which showed that one normal fusion signal and one 3' IGH signal were detected. Thus, submicroscopic deletion of the IGH 5' variable region may have occurred in either the native or rearranged chromosome 14. These findings indicate that B-ALL with IGH rearrangements may be accompanied by submicroscopic deletions of the IGH 5' variable region, which can be detected by FISH. The clinical significance of such deletions is unclear, but the loss of part of the IGH gene in B-ALL warrants further study.

Keyword

IGH deletion; IGH rearrangements; Precursor B lymphoblastic leukemia; FISH

MeSH Terms

Adult
Child
Female
*Gene Deletion
*Gene Rearrangement
Humans
Immunoglobulin Heavy Chains/*genetics
In Situ Hybridization, Fluorescence
Infant
Male
Middle Aged
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/pathology
Young Adult
Immunoglobulin Heavy Chains

Figure

• 

  Fig. 1 Representative fluorescence in situ hybridization patterns using IGH break-apart probes (green signal: IGH 5' variable region; red signal: IGH 3' flanking probe that lies 3' to the constant gene segments). (A) Normal pattern (2 fusion signals) (B) IGH rearrangement and deletion of the IGH 5' variable region in the normal chromosome 14 (1 green and 2 red signals) (C-1) IGH rearrangement without IGH submicroscopic deletion (1 fusion, 1 green, and 1 red signal) (C-2) one normal IGH locus and submicroscopic deletion of the IGH 5' variable region (1 fusion and 1 red signal). It could not be determined whether the IGH submicroscopic deletion developed within normal cells or cells with an IGH rearrangement. (D-1) gain of IGH, suggesting trisomy 14 (3 normal fusion signals) (D-2) gain of IGH, accompanied by IGH rearrangement (2 fusion signals, 1 green and 1 red signal).

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