The Simulation of Hematopoiesis

Abkowitz, Janis L.; Persik, Monica T.; Catlin, Sandra N.; Guttorp, Peter

doi:10.1007/978-1-4613-0391-6_41

Cited by 1 publication

(3 citation statements)

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“…Excessive skewing is not due to HSC depletion or to HSC neoplasia. A reanalysis of previous studies (8,9) suggests that excessive skewing may also develop after busulfan administration. Therefore, caution is required when using X chromosome inactivation patterns to diagnose myelodysplasia in elderly individuals or in patients who have received repeated chemotherapy (6,37,38).…”

Section: Discussionmentioning

confidence: 93%

“…Of interest, a skew in progenitor G6PD phenotype was seen after busulfan administration in three of six cats previously studied, and in each instance, the change was toward the G G6PD phenotype (8). A skew toward G G6PD developed in a fourth animal after the repeated administration of busulfan (9). Because busulfan depletes and damages hematopoietic stem cells to induce aplastic anemia, a similar mechanism could be responsible for the relative growth advantage of cells containing G G6PD.…”

Section: Discussionmentioning

confidence: 96%

“…Each progenitor and differentiated cell expresses the G6PD phenotype of the HSC from which it derived. In previous investigations of female Safari cats in whom hematopoiesis was perturbed by the administration of chemotherapy (busulfan) or by the autologous transplantation of limited numbers of HSCs, we observed fluctuations in the percent of progenitor cells with d G6PD (2,(8)(9)(10)(11). In this report, we analyze data obtained from all female Safari cats before their entry into experimental protocols.…”

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confidence: 98%

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An X chromosome gene regulates hematopoietic stem cell kinetics

Abkowitz

Taboada

Shelton

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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Females are natural mosaics for X chromosome-linked genes. As X chromosome inactivation occurs randomly, the ratio of parental phenotypes among blood cells is approximately 1:1. Recently, however, ratios of greater than 3:1 have been observed in 38-56% of women over age 60. This could result from a depletion of hematopoietic stem cells (HSCs) with aging (and the maintenance of hematopoiesis by a few residual clones) or from myelodysplasia (the dominance of a neoplastic clone). Each possibility has major implications for chemotherapy and for transplantation in elderly patients. We report similar findings in longitudinal studies of female Safari cats and demonstrate that the excessive skewing that develops with aging results from a third mechanism that has no pathologic consequence, hemizygous selection. We show that there is a competitive advantage for all HSCs with a specific X chromosome phenotype and, thus, demonstrate that an X chromosome gene (or genes) regulates HSC replication, differentiation, and͞or survival.

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