CML and Environmental Factors Related to Complex Karyotypes.

Background: Chronic myeloid leukemia (CML) is a clonal disorder of abnormal pluriopotent stem cell characterized by the translocation t(9;22)(q34;q11) that results in a BCR/ABL fusion gene called Philadelphia (Ph) chromosome. Other complex Ph abnormalities or unusual cytogenetic rearrangements have been described and are considered by some researchers to be unfavourable prognosis factors.

Aims: To perform a epidemiological study to consider environmental exposures in patients diagnosed of CML in a northern Spanish area (Aragon) and to evaluate differences among CML patients regarding complex or variant karyotypes versus classic t(9;22)(q34;q11).

Patients and methods: Observational, descriptive and retrospective-prospective study.

Data resources: medical records and data from haematological registry of the Aragon Community. A structured telephone survey was used to evaluate the exposure.

Variables: age, gender, date and place of birth, place of residence, date of diagnosis, Kantarjian score system, cytogenetic characteristics as standard Ph’ or variant translocation, type of therapy, status of disease at the time of study, time to progression and occupational and leisure exposures to toxic products, regular personal use of hair dye, participation in wars, lifestyle, animals, dietary habits, cellular phone use, cigarette smoking, alcoholic beverage and specific recreational drug intake, medical history focused on chemotherapy, radiation therapy, and treatment with isotopes, hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), Zoster Herpes virus (ZHV) and cytomegalovirus (CMV) infection, and personal and familial history of neoplastic disorders. The study was based on a cohort of 67 patients in diagnosed as having CML in chronic phase between 1999–2003. All cytogenetic analysis were performed in the same laboratory and included: standard cytogenetic analysis, fluorescence in situ hybridization using a BCR/ABL specific probe and molecular study by qualitative PCR. Data were introduced into SPSS statistical package 11.0 to perform descriptive statistical, risk analysis and non-parametric tests in order to evaluate differences between classic and complex or variant karyotypes.

Results: 34 males (50.7%) and 33 females (49.3%) were included in the study but only 60 were available to analyze. Mean age 52, range 19–86. Variant or complex kariotypes 14 (23.3%): males 11(78.5%), females 3(21.5%). Typical or classical t(9;22)(q34;q11) 46 (76.7%): males 24 (52.2%), females 22 (47.8%). No statistical differences were found between both groups except for smoking habit. A major number of complex or variant karyotypes was showed in current cigarette smokers with a statistical significance (p=0.004). Most of the subjects with classic translocation reported having pets, mainly dogs (p=0,038). All the subjects with a previous contact with toxic product belong to the group of classical karyotype. These different toxics emerging from the interviews were cobalt, lead, oil-based paints, petrol-derived chemical products, etchings, sulphates, varnishes, glue, PVC, solvents pesticides and benzene.

Conclusion: A remarkable incidence of complex or variant kariotypes have been found in our area: 23.3%. These complex or variant kariotypes were found mainly in men. Smokers showed a higher incidence of variant or complex kariotypes.