Prognostic value of p16INK4a gene deletions in pediatric acute lymphoblastic leukemia

cord blood), women 25 to 32 years old (young women group), and women more than 75 years old (elderly women). The frequency of skewed X inactivation in polymorphonuclear cells (PMNs) increased with age: in fact, a cleavage ratio of at least 3.0 was found in 3 of 36 cord blood samples, 5 of 30 young women, and 14 of 31 elderly women. The inactivation patterns found in T lymphocytes were significantly related to those observed in PMNs in both young (P , .001) and elderly women (P , .01). Based on the above estimates, the probability that the 4 women in our family simply had age-related skewing would be 8 divided by 10 000 [(5 of 30)4], while the probability that skewing was familial is 9992 divided by 10 000. Consequently our conclusion had a strong scientific basis. Aivado et al suggest that a comparison of leukocyte XCIP with XCIP from other tissues is needed. To define the best control tissue for the interpretation of X chromosome inactivation patterns in hematopoietic cells, we previously analyzed X chromosome inactivation patterns in different peripheral blood cell populations and in hair bulbs from healthy women belonging to different age groups.2 When PMNs were compared with hair bulbs,2(Fig3) no relationship was found with respect to the inactivation ratio (r 5 .31, P . .05). There was no difference between young and elderly women in this respect, a cleavage ratio of at least 3.0 in PMNs being associated with a similar value only in about 50% of hair bulb DNA from either young or elderly women. In summary, findings of our study clearly indicate that the most likely explanation of the above findings is that the proband, despite a markedly congenitally unbalanced X chromosome inactivation in her hematopoietic cells, was able to produce normal amounts of red cells for the first 6 decades of her life, as her daughters and granddaughter do. In the seventh decade she developed acquired skewing, as do about one third of elderly women. She unfortunately further inactivated the parental X chromosome carrying the normal ALAS2 gene, and when nearly all red cell precursors expressed the mutant gene, she became severely anemic.