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Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients
OBJECTIVE: The Philadelphia (Ph) chromosome, consisting of the t(9;22)(q34;q11) translocation, is observed in ~90% of patients with chronic myeloid leukemia (CML). Variant Ph translocations are observed in 5%-10% of CML patients. In variant translocations 3 and possibly more chromosomes are involved. Herein we report 6 CML patients with variant Ph translocations.METHODS: Bone marrow samples were examined using conventional cytogenetic meth ods. Fluorescence in situ hybridization (FISH) with whole-chromosome paints and BCR-ABL 1D probes were used to confirm and/or complement the findings, and identify rearrangements beyond the resolution of conventional cytogenetic methods. RESULTS: Variant Ph translocations in the 6 patients were as follows: t(7;22)(p22;q11), t(9;22;15)(q34;q11;q22), t(15;22)(p11;q11), t(1;9;22;3)(q24;q34;q11;q21), t(12;22)(p13;q11), and t(4;8;9;22)(q11;q13;q34;q11).CONCLUSION: Among the patients, 3 had simple and 3 had complex variant Ph translocations. Two of the presented cases had variant Ph chromosomes not previously described, 1 of which had a new complex Ph translocation involving chromosomes 1, 3, 9, 22, and t(1;9;22;3)(q24;q34;q11;q21) apart from a clone with a classical Ph, and the other case had variant Ph translocation with chromosomes 4, 8, 9, and 22, and t(4;8;9;22)(q11;q13;q34;q11) full complex translocation. Number of studies reported that some patients with variant Ph translocation were poor responders to imatinib. All of our patients with variant Ph translocations had suboptimal responses to imatinib, denoting a poor prognosis also. Variant Ph translocations may be important as they are associated with prognosis and therapy for CML patients.

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Authors: Dilhan Kuru, Yelda Tarkan Argüden, Muhlis Cem Ar, Ayşe Çırakoğlu, Şeniz Öngören, Şükriye Yılmaz, Ahmet Emre Eşkazan, Ayhan Deviren, Teoman Soysal, Seniha Hacıhanefioğlu, Birsen Ülkü

Keywords: Kronik myeloid lösemi (KML), varyant Philadelphia kromozomu, sitogenetik, floresan in situ hibridizasyon (FISH)

  • Year: 2011
  • Number: 3
  • Referance No: 16056
  • Figure 1. Partial G-banding karyotypes in the 6 patients. A. Patient 1: t(7;22)(p22;q11). B. Patient 2: t(9;22;15)(q34;q11;q22). C. Patient 3: t(15;22)(p11;q11) and clonal chromosomal changes t(13;15) (p11;q13). D. Patient 4: t(1;9;22;3)(q24;q34;q11;q21). E. Patient 5: t(12;22)(p13;q11). F. Patient 6: t(4;8;9;22)(q11;q13;q34;q11)
  • Figure 2. FISH analysis results. A. Signals of BCR-ABL fusion on interphase cells via the BCR-ABL1 D-FISH probe (ONCOR). Green signals on 1 of chromosome 9, red signals on 1 of chromosome 22, and yellow signals on the Ph chromosome showing BCR-ABL fusion. B. In patient 2 metaphase FISH showing t(9;22;15) via WCP 15 (ONCOR) red signals. C. In patient 4 metaphase FISH showing t(1;9;22;3) via WCP 1, 9, and 22 (MetaSystems). CI. Chromosome 1 is green and chromosome 22 is red. CII. and chhromosome 9 is green and chromosome 22 is red. D. In patient 6 metaphase FISH showing t(4;8;9;22) via WCP 4 and 8, (Cytocell), and WCP 9 and 22 (MetaSystems). DI. Chromosome 4 is green and chromosome 8 is red. DII. Chromosome 4 is green and chromosome 22 is red. DIII. Chromosome 8 is red and chromosome 9 is green

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