PAX5 fusion genes in t(7;9)(q11.2;p13) leukemia: a case report and review of the literature - PubMed (original) (raw)

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PAX5 fusion genes in t(7;9)(q11.2;p13) leukemia: a case report and review of the literature

Dagmar Denk et al. Mol Cytogenet. 2014.

Abstract

Background: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by recurrent genetic alterations including chromosomal translocations. The transcription factor PAX5, which is pivotal for B-cell commitment and maintenance, is affected by rearrangements, which lead to the expression of in-frame fusion genes in about 2.5% of the cases.

Results: Using conventional cytogenetics, fluorescence in situ hybridization (FISH), and molecular methods, an additional case with a der(9)t(7;9)(q11.23;p13) resulting in the expression of a PAX5-ELN fusion gene was identified. Furthermore, a general review of leukemia harboring a t(7;9)(q11.2;p13) or der(9)t(7;9)(q11.2;p13), which occurs more often in children than in adults and shows a remarkably high male preponderance, is given. These cytogenetically highly similar translocations lead to the expression of one of three different in frame PAX5-fusions, namely with AUTS2 (7q11.22), ELN (7q11.23), or POM121 (7q11.23), which constitute the only currently known cluster of PAX5 partner genes.

Conclusion: Our report underlines the recurrent involvement of PAX5 in different fusion genes resulting either from t(7;9)(q11.2;p13) or der(9)t(7;9)(q11.2;p13), which cannot be distinguished cytogenetically and whose discrimination requires molecular analysis.

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Figures

Figure 1

Figure 1

Cytogenetic and molecular genetic analysis of a PAX5-ELN positive case. (A) Karyogram; red arrow indicates the derivative chromosome der(9)t(7;9)(q11.23;p13) (refined karyotype using molecular methods). (B) FISH using _PAX5_-specific BAC clones showing a 3′-end deletion: 5′-end-specific clone (red signals); 3′-end-specific clone (green signals); black and red arrows indicate the normal and derivative chromosome, respectively. (C) FISH using PAX5- and _ELN_-specific BAC clones showing a co-localization: PAX5 5′-end-specific clone (red signals); ELN 3′-end-specific clone (green signals); arrows indicate the normal chromosomes 9 and 12 (white) and the derivative chromosome (black). (D) RT-PCR using primers located in PAX5 exon 2–3 and ELN exon 6 resulting in amplification of PAX5-ELN fusion transcripts. M, molecular weight marker DNA-mix ladder (Peqlab); lane 1, patient No. 5; lane 2, normal control. (E) Sequence chromatogram of the PAX5-ELN fusion junction showing the fusion between exon 7 of PAX5 and exon 5 of ELN.

Figure 2

Figure 2

Schematic representation of the structure of PAX5 and the putative consensus chimeric proteins. PD, paired domain; 8, octapeptide; HD, partial homeodomain; TA, transactivation domain; I, inhibitory domain; P, proline-rich regions; H, histidine-rich regions; KA, alanine-rich cross-linking domains; KP, proline-rich cross-linking domains; HY, hydrophobic domains; 6, VGVAPG hexapeptide domain; C, C-terminal domain; i, insertion; N, POM121 5′-untranslated region; FG, FG-repeats; arrows and filled lollipops indicate nuclear localization signals and fusion breakpoints, respectively.

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