Sex differences in the incidence of chronic myeloid leukemia.

The incidence of chronic myeloid leukemia (CML), which is caused by BCR/ABL chimeric oncogene formation in a pluripotent hematopoietic stem cell (HSC), increases with age and exposure to ionizing radiation. CML is a comparatively well-characterized neoplasm, important for its own sake and useful for insights into other neoplasms. Here, Surveillance, Epidemiology and End Results (SEER) CML data are analyzed after considering possible misclassification of chronic myelo-monocytic leukemia as CML. For people older than 25 years, plots of male and female CML log incidences versus age at diagnosis are approximately parallel straight lines with males either above or to the left of females. This is consistent with males having a higher risk of developing CML or a shorter latency from initiation to diagnosis of CML. These distinct mechanisms cannot be distinguished using SEER data alone. Therefore, CML risks among male and female Japanese A-bomb survivors are also analyzed. The present analyses suggest that sex differences in CML incidence more likely result from differences in risk than in latency. The simplest but not the sole interpretation of this is that males have more target cells at risk to develop CML. Comprehensive mathematical models of CML could lead to a better understanding of the role of HSCs in CML and other preleukemias that can progress to acute leukemia.

A novel t(2;17) in transformation of essential thrombocythemia to acute myelocytic leukemia.

A transformation of essential thrombocythemia to acute myelocytic leukemia (AML), myelodysplastic syndrome, or agnogenic myelocytic metaplasia is a relatively rare event. It occurs in 1%-4.5% of all patients with either treated or untreated essential thrombocythemia. Cytogenetic changes in the transformation to AML are common. We report the case of a patient treated for essential thrombocythemia with hydroxyurea for 49 months. He developed AML with a t(2;17), which to our knowledge has not been described in the literature.

Alexander I. Ignatowski: a pioneer in the study of atherosclerosis.

In 1908, Alexander I. Ignatowski (1875-1955) published his pioneering work that first revealed a relationship between cholesterol-rich food and experimental atherosclerosis. This early experimental work paved a way to the metabolic study of the mechanism of atherosclerosis. Herein, we present a brief account of Ignatowski's work and life.

Size of the protein-coding genome and rate of molecular evolution.

In diploid populations of size N, there will be 2 Nmu mutations per nucleotide (nt) site (or per locus) per generation (mu stands for mutation rate). If either the population or the coding genome double in size, one expects 4 Nmu mutations. What is important is not the population size per se but the number of genes (coding sites), the two being often interconverted. Here we compared the total physical length of protein-coding genomes (n) with the corresponding absolute rates of synonymous substitution (K(S)), an empirical neutral reference. In the classical occupancy problem and in the coupons collector (CC) problem, n was expressed as the mean rate of change (K(CC)). Despite inherently very low power of the approaches involving averaging of rates, the mode of molecular evolution of the total size phenotype of the coding genome could be evidenced through differences between the genomic estimates of K(CC) [K(CC)=1/(ln n + 0.57721) n] and rate of molecular evolution, K(S). We found that (1) the estimates of n and K(S) are reciprocally correlated across taxa (r=0.812; p<< 0.001); (2) the gamete-cell division hypothesis (Chang et al. Proc Natl Acad Sci USA 91:827-831, 1994) can be confirmed independently in terms of K(CC)/K(S) ratios; (3) the time scale of molecular evolution changes with change in mutation rate, as previously shown by Takahata (Proc Natl Acad Sci USA 87:2419-2423, 1990), Takahata et al. (Genetics 130:925-938, 1992), and Vekemans and Slatkin (Genetics 137:1157-1165, 1994); (4) the generation time and population size (Lynch and Conery, Science 302:1401-1404, 2003) effects left their "signatures" at the level of the size phenotype of the protein-coding genome.