MLL-AF4 fusion is the most common consequence of chromosomal translocations in infant leukaemia and is associated with a poor prognosis. MLL-AF4 is thought to be required in haematopoietic stem cells to elicit leukaemia and may be involved in tumour phenotype specification as it is only found in B-cell tumours in humans. We have employed the invertor conditional technology to create a model of MLL-AF4, in which a floxed AF4 cDNA was knocked into Mll in the opposite orientation for transcription. Cell-specific Cre expression was used to generate Mll-AF4 expression. The mice develop exclusively B-cell lineage neoplasias, whether the Cre gene was controlled by B-or T-cell promoters, but of a more mature phenotype than normally observed in childhood leukaemia. These findings show that the MLL-AF4 fusion protein does not have a mandatory role in multi-potent haematopoietic stem cells to cause cancer and indicates that MLL-AF4 has an instructive function in the phenotype of the tumour.

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Background RCTs demonstrated the newest LTBI regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), as efficacious as 9 months of isoniazid (9H) with a greater completion rate (82% versus 69%); however, 3HP has not been assessed in routine health care settings. Methods Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions (ADRs), and factors associated with treatment discontinuation. Results Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children 2–17 years had the highest completion rate, 94.5% (155/164). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% CI, 0.23–0.85]; P = .014), and highest in persons ≥65 years (RR, 1.72 [95% CI, 1.25–2.35] P = .001). In multivariable analyses, discontinuation was lowest among contacts of patients with TB disease (adjusted relative risk [ARR], 0.68 [95% CI, 0.52–0.89]; P = .005), and students (ARR, 0.45 [95% CI, 0.21–0.98]; P = .044); highest with incarceration (ARR, 1.43 [95% CI, 1.08–1.89]; P=.013) and homelessness (ARR, 1.72 [95% CI, 1.25–2.39]; P = .001). ADRs were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions Completion of 3HP in routine health care settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

Tuberculosis case rates in prison systems remain higher than in the general population. Inmates with TB are less likely than noninmates to complete treatment.

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