Objective: To analyze the association of cytogenetic abnormalities with the prognosis of chronic myeloid leukemia (CML) patients in tyrosine kinase inhibitors (TKI) era. Methods: Karyotype analysis of chromosome G-banding was carried out in 387 newly diagnosed CML patients by short-term culture of bone marrow cells. The correlation of cytogenetic abnormalities and CML progression was explored in combination with ABL tyrosine point mutations. Result: Of 387 patients with positive BCR-ABL fusion gene assayed by fluorescence in situ hybridization (FISH) technique, 94.1% (364/387) patients were Ph positive and 5.9% (23/387) Ph negative; 320 patients (87.9%) had a translocation t (9;22) (q34;q11) and 5 (1.4%) a variant translocation t (v;22) . Additional cytogenetic aberrations (ACA) at diagnosis were found in 10.7% (39/387) Ph⁺ patients, major route ACA in 22 (56.4%) cases and minor route ACA in 15 (38.5%) cases and 2 patients (5.1%) lacked the Y chromosome (−Y) ; 23.4% (71/303) patients occurred ACA during TKI treatment and the most frequent abnormalities were abnormal chromosome numbersd, which were likely associated with high proportion of disease progression (χ²=168.21, P<0.001) and ABL tyrosine point mutations (χ²=29.04, P<0.001) . Newly diagnosed CML-CP patients with t (9;22) (q34;q11) had a longer event-free survival (EFS) and disease-free survival (DFS) rates than that of patients with ACA (P=0.037; P=0.003) , while the overall survival (OS) had no significant differences (P=0.209) . As for CML-CP patients that occurred ACA during TKI therapy would have a marked low OS, EFS and DFS (all P<0.001) compared with no ACA occurred patients. Survival of advanced patients that occurred ACA were dramatically reduced. Conclusion ACA often emerged during the disease progress in CML patients, regular and timely detection of chromosomes karyotype and ABL tyrosine point mutations during TKI treatment was important for therapeutic evaluation, progress and prognosis of CML.

Objective: To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) . Methods: Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph⁺ ALL patients with p16 deletion. Results: Of 80 adult Ph⁺ ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×10⁹/L) and CD20 expression. The incidence of complex chromosome abnormality in p16 gene deletion group was higher than that in non-deletion group, with alternations in chromosome 7, 8, 19 and der (22) more frequently observed. There was no difference occurred between patients with or without p16 gene deletion in complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs) . However, after three cycles of chemotherapy, the MMR and CMR rate in the p16 gene deletion group was lower than patients with wild-type p16 gene (P=0.034, P=0.036) . The p16 gene deletion patients showed no significant differences in MMR, CMR and relapse rate between Imatinib or Dasatinib plus chemotherapy (P>0.05) . Deletion of p16 gene was significantly associated with poor outcomes including worse overall survival (OS) (37.1% vs 54.1%, P=0.037) , lower disease free-survival (DFS) (12.4% vs 45.9%, P=0.026) , and increased cumulative incidence of relapse (P=0.033) . Among the 25 patients with p16 deletion, 14 underwent allo-HSCT and the median survival was 21 months, better than that of patients received chemotherapy alone (12 months) (P=0.030) . Conclusion This study indicated that deletion of p16 was associated with poor prognosis in adult Ph⁺ ALL, and the utility of second-generation TKI (Dasatinib) does not necessarily have an edge on efficacy over Imatinib, but allo-HSCT has the potential of elongating life expectancy. It is an important significance to define the status of p16 in Ph⁺ ALL for predicting prognosis and guiding therapy decision-making.

Objective To investigate the relationship and potential pathways between metal(loid)exposure and the risk of polycystic ovary syndrome(PCOS)in women of childbearing age. Methods This case-control study included 200 patients with PCOS(cases)and 896 non-PCOS controls with the age of 25-37 years.The concentrations of 29 metal(loid)s in the follicular fluid(FF)and clinical indicators in the serum were measured in all participants.Logistic regression analysis and mediation analysis were conducted to evaluate the associations between metal(loid)exposure and PCOS risk and investigate the possible roles of clinical indicators,respectively. Results Logistic regression analysis revealed an association between high copper levels in FF and increased PCOS risk(highest vs.lowest quartile:adjusted odds ratio=2.94,95%confidence interval:1.83-4.72).A high luteinizing hormone/follicle-stimulating hormone ratio and elevated levels of testosterone and anti-Müllerian hormone(AMH)were strongly associated with increased PCOS risk induced by high copper exposure.The mediation analysis indicated a mediating effect of AMH in the association between copper exposure and PCOS risk. Conclusion Copper may affect PCOS risk through the hypothalamic-pituitary-ovarian axis,mediated by AMH.Copper exposure and internal AMH levels are important indicators for early warning of PCOS development.