Preclinical efficacy of azacitidine and venetoclax for infant KMT2A-rearranged acute lymphoblastic leukemia reveals a new therapeutic strategy.

Infants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL) have a dismal prognosis. Survival outcomes have remained static in recent decades despite treatment intensification and novel therapies are urgently required. KMT2A-rearranged infant ALL cells are characterized by an abundance of promoter hypermethylation and exhibit high BCL-2 expression, highlighting potential for therapeutic targeting.

Preclinical Evaluation of Carfilzomib for Infant -Rearranged Acute Lymphoblastic Leukemia.

Background: Infants with -rearranged B-cell precursor acute lymphoblastic leukemia (ALL) have poor outcomes. There is an urgent need to identify novel agents to improve survival. Proteasome inhibition has emerged as a promising therapeutic strategy for several hematological malignancies.

New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment.

The microenvironments of leukemia and cancer are critical for multiple stages of malignancies, and they are an attractive therapeutic target. While skeletal abnormalities are commonly seen in children with acute lymphoblastic leukemia (ALL) prior to initiating osteotoxic therapy, little is known about the alterations to the bone marrow microenvironment during leukemogenesis. Therefore, in this study, we focused on the development of precursor-B cell ALL (pre-B ALL) in an immunocompetent BCR-ABL1 model.

APOE genotype results in differential effects on the peripheral clearance of amyloid-beta42 in APOE knock-in and knock-out mice.

The epsilon4 allele of apolipoprotein E (APOE) is currently the major genetic risk factor identified for Alzheimer's disease (AD). Previous in vivo data from our laboratory has demonstrated that amyloid-beta (Abeta) is rapidly removed from the plasma by the liver and kidney and that the rate of its clearance is affected by ApoE in C57BL/6J and APOE-/- mice. To expand upon these findings, we assessed the peripheral clearance of human synthetic Abeta42 in APOE epsilon2, epsilon3, and epsilon4 knock-in and APOE knock-out mice injected with lipidated recombinant apoE2, E3, and E4 protein.

Changes in vasotocin immunoreactivity of paraventricular nuclei and adrenal function of Japanese quail in relation to different phases of sexual development.

In relevance to osmoregulatory and reproductive functions, activity of hypothalamic neurosecretory neurons may also vary seasonally. The current study was performed to determine annual changes in ir-AVT neurons of hypothalamus and adrenal gland function. We examined changes in ir-AVT neuron by immunohistochemical method and plasma testosterone was measured by enzyme immunoassay.

Effect of long and short photoperiod on vasotocin neurons of paraventricular nuclei and adrenal function of water deprived Japanese quail.

The responses of magnocellular neurons of paraventricular nuclei (PVN) and changes to adrenal activity to water deprivation in Japanese quail maintained under gonado-inhibitory and stimulatory photoperiods were examined. Water deprivation of 4 days resulted in a 12% decrease in body weight of sexually regressed short day (SD, 6L:18D) quail, while the decrease was more (18%) in sexually stimulated long day (LD, 16L:8D) quail. The increase in plasma osmolality following water deprivation was also more (47%) in LD than to SD quail (36%).