Standard and variant Philadelphia translocation in a CML patient with different sensitivity to imatinib therapy

AbstractMost chronic myeloid leukemia (CML) patients show the Philadelphia chromosome (Ph) arising from the reciprocal t(9;22), but 5–10% present variants of this translocation involving different breakpoints besides 9q34 and 22q11.We report the non simultaneous occurrence of two different types of Ph translocation in a CML patient: a t(9;22)(q34;q11) standard and a three-way variant t(9;11;22)(q34;p15;q11).Bone marrow cells with standard translocation did not have BCR/ABL kinase domain (KD) mutations and were sensitive to imatinib therapy. In contrast, bone marrow cells with the variant translocation showed two BCR/ABL KD mutations and were resistant to imatinib, thus inducing transformation to the blast phase and karyotype evolution