Isochromosome (X)(p10) in hematologic disorders: FISH study of 14 new cases show three types of centromere signal...

Though X chromosome anomalies are uncommon in hematologic malignancies, isodicentric X chromosomes, idic(X)(q13), with break and fusion points at Xq13 are well known among older females with de novo myelodysplasia. In contrast, only 17 patients with X isochromosomes involving break and fusion points at the centromere i(X)(p10) have been published, to our knowledge. We present 14 new patients with i(X)(p10) identified by G-banding and further characterized by fluorescence in situ hybridization (FISH) using probes for the X p-arm, X alpha-satellite DNA (DXZ1), and the XIST gene (Xq13). These anomalies each had an X p-arm probe signal on either side of a single centromeric FISH signal, thus they are monocentric isochromosomes. On the basis of FISH, the following three centromeric patterns were identified: (1) centromere signal same size as normal X, (2) centromere signal larger than normal X, and (3) centromere signal smaller than normal X. These centromere patterns may be related to the mechanism of i(X)(p10) formation. In 9 (64%) of 14 patients, the i(X)(p10) was the sole anomaly, attesting to its pathogenic potential. Our series, when collated with information on previously reported cases of i(X)(p10), show that this anomaly is associated with females with a median age 74 years, though patients from 3.75 to 49 years, including a 17-year-old in the present cohort, have been described. i(X)(p10) is observed in a wide range of hematologic malignancies, including myeloid and lymphoid disorders, as well as a patient with therapy-related AML in the present series. i(X)(p10) has been reported in occasional males, indicating that this anomaly can arise from active X chromosomes. It is not known whether i(X)(p10) arises randomly from the active or inactive X chromosome in female patients.