The response of Philadelphia chromosome (Ph(+)) acute lymphoblastic leukemia (ALL) to treatment by BCR-ABL tyrosine kinase inhibitors (TKIs) has been disappointing, often resulting in short remissions typified by rapid outgrowth of drug-resistant clones. Therefore, new treatments are needed to improve outcomes for Ph(+) ALL patients. In a mouse model of Ph(+) B-lineage ALL, MCL-1 expression is dysregulated by the BCR-ABL oncofusion protein, and TKI treatment results in loss of MCL-1 expression prior to the induction of apoptosis, suggesting that MCL-1 may be an essential prosurvival molecule. To test this hypothesis, we developed a mouse model in which conditional allele(s) of Mcl-1 can be deleted either during leukemia transformation or later after the establishment of leukemia. We report that endogenous MCL-1's antiapoptotic activity promotes survival during BCR-ABL transformation and in established BCR-ABL(+) leukemia. This requirement for MCL-1 can be overcome by overexpression of other antiapoptotic molecules. We further demonstrate that strategies to inhibit MCL-1 expression potentiate the proapoptotic action of BCL-2 inhibitors in both mouse and human BCR-ABL(+) leukemia cell lines. Thus, strategies focused on antagonizing MCL-1 function and expression would be predicted to be effective therapeutic strategies.

A high frequency of HBV infection was seen using molecular methods in thalassemic patients. The frequency of infection was similar in vaccine responders and non-responders. A number of mutations were observed in the S gene, which could have implications for viral replication as well as virus-host cell interaction.

Frequency of H. pylori as detected using endoscopy and serology-based tests is not higher among patients with GN as compared with controls in India.

Objectives Inflammation plays a major role in pathogenesis of cervical cancer. We planned to study whether polymorphisms in inflammation-related genes, IL-1RN (VNTR) and IL-1b (-511C/T), are associated with risk of cervical cancer.Design Case-control study.Setting Uttar Pradesh state in India.Sample One hundred and fifty, histopathologically confirmed cases with cervical cancer and 162 age-, ethnicity-matched, cervical cytology negative, healthy controls were recruited to this study.Methods Genotyping of IL-1RN (VNTR) and IL-1b (-511C/T) polymorphisms was performed using polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism. Power of study was 80% with type 1 error of 0.05. Haplotypes frequencies were obtained by computer package 'Arlequin'.Main outcome measures Haplotype IL-1RN*2/IL-1b*T is associated with higher risk and of cervical cancer.Results IL-1RN genotypes 1/2 and 2/2 were associated with significantly elevated risk of cervical cancer (OR = 3.3; P = 4.9 · 10 -6 and OR = 2.9, P = 0.02). Similarly, TT genotype of IL-1b polymorphism was significantly higher in cases compared with controls (57.7 versus 38.3%; OR = 2.8; P = 0.012). 2/2 genotype of IL-1RN (OR = 4.8, P = 0.0006) and TT genotype of IL-1b (OR = 5.2; P = 0.02) were associated with the higher stages (III) of cervical cancer. Haplotypes 1T (IL-1RN*1/IL-1b*T) and 2T (IL-1RN*2/IL-1b*T) were also significantly associated with higher susceptibility to cervical cancer and its progression. Logistic regression analysis suggests IL-1RN allele 2 and IL-1b -511T were independently associated with increased risk for cervical cancer.Conclusion IL-1RN*2 and IL-1b -511*T in various combinations of genotypes and haplotypes are associated with higher susceptibility for cervical cancer.

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1. The primary antibody response to sheep erythrocytes was determined by haemagglutination test in guinea fowl. The effects of various genetic and non-genetic factors on immune response to sheep RBCs in guinea fowl were also estimated. 2. The immune response to sheep RBCs was normally distributed in guinea fowl with mean titre at 1.534 +/- 0.014. 3. In guinea fowl, effects on titre values of sire and variety (feather colour) were significant whereas sex and sex x variety interaction effects were non-significant. 4. The estimate of heritability for immune response to sheep RBCs in guinea fowl was 0.35 +/- 0.17.