Frequency and Diversity of Variant Philadelphia Chromosome In Chronic Myeloid Leukemia Patients
Authors: Chauffaille Maria de Lourdes L. F. , Ameida Ana C , Martinez Rosana M , Silva Aline S G 
Published: October 2019

Abstract
Abstract 4903
The Philadelphia chromosome (Ph), t(9;22), is detected in around 90% of the chronic myeloid leukemia (CML) patients, but in the remaining 5–10% cases a variant type may be present. Variant Ph-chromosome is characterized by the involvement of another chromosome in addition to the 9 and 22. It can be a simple type of variant when one more chromosome is involved, or complex, in which two or more chromosomes take part in the translocation. The aim of this report is to relate the diversity of variants Ph found in CML patients at the Cytogenetic service of Fleury Lab (São Paulo, Brazil) during the past 12 years. All Ph-positive CML patients (ALL&AML were excluded) were surveyed and the variant Ph ones were listed. All the karyotype analysis were from non-stimulated short term cultures of bone marrow or peripheral blood and classified according to ISCN (1999-2009). Of the 1,071 Ph-positive cases, 967 were classic Ph, while 50 (5.17%) were variants. Regarding the variant form, 44 (88%) were simple type and 6 (12%) complex type (table 1), similar to Marzocchi et al (2011), who found 93% and 7% of each type, respectively. Some of the variant Ph translocations we detected are listed in table 1. In agreement with what Marzocchi et al reported, the most involved chromosome was the 17 (eleven times in the present report and four cases in theirs), followed in frequency by the chromosome 1 (six times), 20 (five times), 6, 11 (four times each), and 2, 10, 12 and 15 (three times each). The chromosomes not involved in the Ph translocation were: 8, 9, 18, 21, 22, X and Y (Figure 1). Among all breakpoints seen in this survey, six were repeated: 11p15, 14q32, 15q11.2, 16p13.1, 17p13 e 17q21, differing from Marzocchi et al who denied finding any recurrent breakpoint. Reid et al. (2003) listed nine recurring breakpoints in variant Ph translocations most reported by other authors, who also assert that most of breakpoints related to variant Ph occur in regions of known oncogenes or typical secondary breakpoints in other cancers. Indeed we endorse this statement, since we also found some breakpoints related to other cancers. Of the list Reid et al reported, three were found in this study as well: 12p13, 17p13 and 17q21. Some of the genes located in these regions are related to other cancers (i.e. ETV6, CD9, RARA, GAS7). However, the gene TP53, located in the region 17p13 was the only one previously reported as related to CML. Oliver M. (2007) states that this gene is involved in 20–30% of cases of blast crisis CML. Regarding the prognosis, evolution of the disease and response to the treatment, it seems that variant type of Ph translocation has no implication for survival (Marzocchi et al 2011 and Maha et al 2004. In conclusion, as we presented a large variety of variant Ph translocations, it becomes clear that there are lots of possible interactions to form variant type and most of them occur in regions already reported as oncogenes or related to cancers, indicating that there must be local phenomena favoring the predisposition to these breakpoints involvement.Table 1–Examples of variant Ph karyotypes found in this survey, showing a little of the diversity of interaction.Karyotype46,XY,t(1;9;22;16)(q32;q34.1;q11.2;p13)[2]/46,XY46,XX,t(9;22;1;13)(q34.1;q11.2;p12;q34)[17]/46,XX[3]46,XY,t(9;22;1;?3)(q34.1;q11.2;q36.3;?q26)[20]46,XX,t(1;9;22;14)(p21;q34.1;q11.2;q32)[20]46,XY,t(9;22;2)(q34.1;q11.2;q24)[8]/46,XY[12]46,XY,t(9;22;4)(q34.1;q11.2;p16)[20]46,XY,t(9;22;5)(q34.1;q11.2;p13)[20]46,XY,t(9;22;6)(q34.1;q11.2;q22)46,XX,t(9;22;7)(q34.1;q11.2;p22)[20]46,XY,t?(9;22;10;11)(q34.1;q11.2;q22;q25)[20]46,XY,t(9;22;12)(q34.1;q11.2;p13)[20]46,XY,t(9;22;14)(q34.1;q11.2;q32)[19]/46,XY[1]46,XY,t(9;22;15)(q34.1;q11.2;q11.2)[20]46,XX,t?(9;22;16)(q34.1;q11.2;p13.3)[20]46,XY,t(9;22;17)(q34.1;q11.2;p13)[20]46,XY,t(9;22;19)(q34.1;q11.2;q11.2)[20]46,XY,t(1;7)(p22;q22),t(9;22;20)(q34.1;q11;q11.2)[2]/46,XY[18]Figure 1– Distribution of chromosomes involved in variant Ph translocation, according to the chromosome region (p arm or q arm).Figure 1. – Distribution of chromosomes involved in variant Ph translocation, according to the chromosome region (p arm or q arm).

Disclosures:
No relevant conflicts of interest to declare.