**3. Variant complex and multiway translocations of Ph chromosome**

#### **3.1 Variant complex translocation of Ph chromosome**

Cytogenetically, CML is characterized by the Ph chromosome formed by the fusion gene of the reciprocal translocation t(9:22)(q34;q11), resulting in the chimeric gene breakpoint cluster region (BCR)-Abelson leukemia (ABL).

Studies demonstrated that approximately 90–95% CML patients have Ph chromosome from the classical reciprocal translocations. However, about 5–10% CML cases have variant types of the Ph chromosome. The variant Ph chromosome translocations are involving chromosomes other than 9 and 22 or multiple chromosomes involved in CML cases [25]. Some studies also suggested that the classical and variant Ph chromosome translocations in CML patient have showed different sensitivities to treatment [26].

Mysorekar et al. reported five male CML cases with variant Ph chromosome translocations. Two cases were two-way translocations, t(16;22), t(15;22), and three cases were three-way translocations, t(1;9;22), t(9;9;22), t(9;14;22), and all cases studied were with BCR-ABL fusion gene, but responded well to the tyrosine kinase inhibitors, imatinib treatment in their studied cases [27].

#### **3.2 Three-way translocation of Ph chromosome**

Three-way translocation involves three chromosomes including the Ph chromosome. Such complex translocation was found not only in adult but also in childhood.

Lee reported a 22-year-old male CML case with a three-way translocation involving in chromosomes 9, 22, and 11 at the breakpoints of q34;q11.2;q24 detected by using cytogenetic-G banding and FISH techniques, and this patient responded well to TKI treatment imatinib [28].

Asif groups reported male CML case with a three-way translocation involving chromosomes 9, 11, and 22 at the breakpoints of q34;p15;q11 in separate studies [29].

Allen-Proctor group reported a male CML case with a three-way translocation involved in chromosomes 9, 22, and 17 at the breakpoints of q34;q11.2;q12 detected by using cytogenetic analysis of G banding and FISH [30].

Most three-way translocations reported were primary abnormalities. Achkar et al. reported a male CML case with a three-way translocation involved in chromosomes 9, 10, and 22 at the breakpoints of q34;p11.2;q11.2 and also loss of Y chromosome as a secondary abnormality after the classical Ph translocation of t(9;22) followed by chemotherapy [31].

CML is very low in childhood and infant. Three-way translocation of Ph chromosome in infant is extremely rare. An 10-month-old boy infant with three-way Ph translocations involved in chromosomes 9, 22, and 14 at the breakpoints of q34;q11.2;q32 by using GTG banding and FISH techniques and confirmed the presence of BCR-ABL by

RT-PCR was reported as the first case with the accelerated phase and received favorable response with hydroxyl urea and the TKI (dasatinib) [32].
