Molecular basis of aggressive disease in chronic lymphocytic leukemia patients with 11q deletion and trisomy 12 chromosomal abnormalities

In B-cell chronic lymphocytic leukemia (CLL), Rai stage, immunoglobulin gene mutational status, chromosomal abnormalities, CD38 and ZAP-70 expression were used as prognostic markers. In this study, to understand the molecular basis of chromosomal abnormalities leading to tumor progression, 90 CLL patients were grouped into poor prognosis (with 11q deletion and trisomy 12) and good prognosis (with normal karyotype and 13q deletion) and their clinical outcome was assessed. Gene expression profiles of 35 CLL samples with poor outcome (11q deletion, n=9; trisomy 12, n=5) and good outcome (13q deletion, n=13; normal karyotype, n=8) were analyzed using oligonucleotide microarray. Significance analysis of microarray (SAM) identified 27 differentially expressed genes between these two subgroups with significant overexpression of ATF5 and underexpression of CDC16, PCDH8, SLAM, MNDA and ATF2 in CLL patients with poor outcome. ATF5 gene expression in CLL was further studied because of its role in the regulation of cell cycle progression/differentiation and apoptosis. The overexpression of ATF5 was confirmed by real-time PCR using 39 CLL samples from the poor and good outcome groups. ATF5 was significantly (p<0.001) overexpressed in the poor outcome group. Furthermore, ATF5 expression was significantly higher in the 11q deletion as well as trisomy 12 group alone compared to the 13q deletion and normal karyotype groups. ATF5 overexpression was also associated with significantly (p=0.04) shorter time to treatment. Similarly, expression of five underexpressed genes also correlated with longer time to treatment. Thus, this report demonstrates that ATF5 may be one of the key genes involved in increased proliferation and survival in 11q deletion or trisomy 12, whereas CD16, CD86, SLAM, MNDA and ATF2 may be involved in the decreased proliferation of CLL cells with 13q deletion or normal karyotype.     

The myeloid transcription factor KLF2 regulates the host response to polymicrobial infection and endotoxic shock

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Highlights? KLF2 deficiency confers a proinflammatory phenotype to myeloid cells ? Myeloid KLF2 deficiency renders animals resistant to polymicrobial infection ? Myeloid KLF2 deficiency renders animals susceptible to endotoxic shock ? KLF2 negatively regulates the NF-κB-HIF-1α axis in macrophages     

A study of mono-neuritic lesions in a leprosy clinic.

An analysis of 11,581 leprosy patients registered at the Acworth Leprosy Hospital clinic showed that 494 cases (4.3%) had primary polyneuritic leprosy and 143 (1.2%) localised cutaneous anaesthetic lesions (or non-visible anaesthetic lesions), accounting for 5.5% who had no evidence of obvious skin lesions.     

Sensitisation by mycobacteria and the effects of BCG on children attending schools in the slums of Bombay

Quadruple skin testing with new tuberculins was used to evaluate the effects of previously administered BCG Madras in children attending schools in the slums, or living in Kopri Leprosy Colony in Bombay. There were differences between schools both in the level of sensitisation of children without BCG scars and in the effects of BCG vaccination. Results obtained at one school resembled those obtained in a previous study in Agra, where BCG was thought to be ineffective. Results from the other schools and Kopri were more like those previously reported from Ahmednagar, where BCG was considered to be much more effective. Thus within the same city groups of children of the same social status may vary widely both in their contact with mycobacteria and in their capacity to benefit from BCG vaccination.