Disproportionate Sex Chromosome Loss in Abnormal Karyotypes of Male and Female Patients with Diagnoses of Myeloid or Lymphoid Neoplasms

Sex chromosome loss (SCL) occurs in different types of human cells and is likely related to aging, but could also be related to other factors. We reviewed cytogenetic studies of bone marrow samples from patients (males and females) with clinical diagnoses of either myeloid or lymphoid delineation in order to establish if SCL is associated with abnormal karyotypes found in these malignancies. Prevalence of clonal SCL (POC-SCL = % cases having ≥ 3 cells with SCL/study) was evaluated retrospectively in a total of 9,593 bone marrow cytogenetic studies performed in our laboratory during a recent calendar year. Results from this database were identified as normal or abnormal karyotypes, as male or female patients, and as having a myeloid or a lymphoid diagnosis. POC-SCL values were determined for each of these designations. Student-t tests were then applied to ascertain if POC-SCL values were significantly different with respect to these three variables. Our statistical analyses showed that: 1) POC-SCL was higher in abnormal than in normal karyotypes. This was true for abnormal male and female karyotypes in both myeloid and lymphoid disorders, compared to cases with normal karyotypes. 2) POC-SCL values were higher in male karyotypes for normal and abnormal myeloid cases, than in females. This was also true in normal karyotypes of lymphoid cases, but had similarly high values for both genders in abnormal karyotypes of lymphoid cases. 3) POC-SCL was about the same in total myeloid versus total lymphoid cases. However, closer examination indicated a higher POC-SCL value was seen in lymphoid patients with normal male and female karyotypes than for myeloid patients with normal male and female karyotypes. Interestingly, POC-SCL was higher in the abnormal myeloid male karyotypes than in the normal male karyotypes, while it was higher in abnormal lymphoid female karyotypes than in the normal female karyotypes. Although clonal-SCL may not reflect a primary biological marker associated with these cancers, our results clearly show that clonal-SCL segregates selectively with abnormal karyotypes associated with myeloid and lymphoid malignancies. Moreover, not only is there a disproportionate over-representation of -Y in abnormal karyotypes, but –X is also a significantly frequent finding in abnormal karyotypes of these diseases.