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. 2012 Aug 20;5(1):36.
doi: 10.1186/1755-8166-5-36.

A novel dic (17;18) (p13.1;q11.2) with loss of TP53 and BCR/ABL rearrangement in an Imatinib resistant chronic myeloid leukemia

Walid Al-Achkar  1 , Abdulsamad Wafa, Faten Moassass, Moneeb Abdullah Kassem Othman
Affiliations

A novel dic (17;18) (p13.1;q11.2) with loss of TP53 and BCR/ABL rearrangement in an Imatinib resistant chronic myeloid leukemia

Walid Al-Achkar et al. Mol Cytogenet. .

Abstract

Background: The so-called Philadelphia (Ph) chromosome is present in more than 90% of chronic myeloid leukemia (CML) cases. It results in juxtaposition of the 5' part of the BCR gene on chromosome 22 to the 3' part of the ABL gene on chromosome 9. Since the majority of CML cases are currently treated with Imatinib, variant rearrangements in general have no specific prognostic significance, although the mechanisms involved in resistance to therapy have yet to be investigated. The T315I mutation within the abl-gene is the most frequent one associated with resistance to tyrosine kinase inhibitors.

Results: This study evaluated a Ph chromosome positive CML case resistant to imatinib mesylate. A dic(17;18), loss of TP53 gene, co-expression of b2a2 and b3a2 fusions transcript and a T315I mutation were found.

Conclusions: We reported here a novel case of a Ph chromosome positive CML with a secondary abnormality [dic(17;18)], resulting to Glivec resistance but good response to nilotinib. The dic(17;18) might be a marker for poor prognosis in CML. Our finding indicated for an aggressive progression of the disease. The patient died under the treatment due to unknown reasons.

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Figures

Figure 1
Figure 1
GTG-banding revealed a complex karyotype with two further aberrant chromosomes besides chromosomes 9 and 22. All derivative chromosomes are highlighted by arrow heads.
Figure 2
Figure 2
Karyotype and chromosomal aberrations were confirmed using molecular cytogenetic approaches. (A) FISH using probes for BCR (green) and ABL (red) confirmed Ph chromosome presence. (B) FISH with CEP 17 (red) and CEP18 (green) showed the presence of both centromeres on the derivative chromosome in question, indicating a dic(17;18). (C) The deletion of TP53 of der(17)(p13.1) was identified using 17p13 (p53) together with a CEP 17 probe. (D) The application of aMCB 17 and 18 characterized the dic(17;18)(p13.1;q11.2) comprehensively . Abbreviations: # = chromosome; der = derivative chromosome; Ph = Philadelphia-chromosome.
Figure 3
Figure 3
Gel electrophoresis of the nested RT-PCR products. Line M, 100 bp molecular weight marker; line 1, negative control; line 2, positive control (b3a2) 353 bp and line 3, coexpression of b2a2 (104 bp) and b3a2 (353 bp) from the patient.
Figure 4
Figure 4
Gel electrophoresis of the DdeI restriction analysis on the ABL exon 7 and progressive appearance of the T315I point mutation. A single base change from C to T results in a fragment length polymorphism. The T315I mutation resulted in an uncut PCR product of 72 bps. Lines 1 and 4, 25 bp molecular weight markers; line 2, T315I mutation from the patient and line 3, normal control (K562 cell line).
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