The treatment of chronic myeloid leukemia (CML) has seen several major advances over the past 30 years, notably with the introduction of interferon followed by Bcr-Abl tyrosine kinase inhibitors. We analyzed trends in the incidence of CML and patient survival in France. All cases recorded in five population-based registries between 1980 and 2009 were included. European (ESR) and world (WSR) standardized incidence rates as well as relative survival (RS) rates were estimated. We analyzed data for 781 patients (9863/3: 13.6%; 9875/3: 82.2%; 9876/3: 4.2%). ESR was 1.02 [95% confidence interval (CI) = 0.93-1.11] and WSR was 0.81 [95% CI = 0.72-0.90]. The five RS rates among patients with Philadelphia chromosome positive (Ph+) CML were 43.7% [30.9-61.9] when diagnosed in 1980-1986, 63.8% [56.9-71.5] in 1987-1999 and 88.7% [84.5-93.0] in 2000-2009. The 8-year RS rate of patients with Ph+ CML diagnosed in 2000-2009 was 83.3% [77.5-89.4]. Therapeutic innovations have thus led to a significant increase in long-term survival in the general CML patient-population.
The sheep immunoglobulin heavy chain Igh-J locus has been characterized in order to determine the genomic organization of JH segments and their contribution to heavy chain diversity. The locus contains six segments, of which two are functional and four are apparently pseudogenes. These segments span a 1.8 kilobase (kb) region. The distance between JH-ps4 (the 3'-most segment) and the first domain of the mu-chain encoding constant gene is about 5 kb. The two functional JH segments have a standard upstream recombination signal sequence, including heptamer and nonamer sequences separated by a 22-23 nucleotide spacer, and end with a RNA donor splice site. These two segments possess all the characteristic JH invariant residues and are found in expressed mu heavy chain variable regions. The 5' functional JH1 segment is used in more than 90% of the cDNAs sequenced to date. The contribution of JH segment germline multiplicity to variable regions diversity appears therefore to be minimal. Comparison with other mammalian JH segments shows that all loci are very closely related and probably have evolved from a common ancestral locus.
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