Enucleation of mammalian erythroblasts is a process whose mechanism is largely undefined. The prevailing model suggests that nuclear extrusion occurs via asymmetric cytokinesis. To test this hypothesis, we treated primary erythroblasts with inhibitors of cytokinesis, including blebbistatin, hesperadin, and nocodazole, and then assayed for enucleation. Although these agents inhibited cell-cycle progression and subsequent enucleation when added early in culture, they failed to block enucleation proper when added to postmitotic cells. These results suggest that contraction of the actomyosin ring is not essential for nuclear expulsion. Next, by ultrastructural examination of primary erythroblasts, we observed an accumulation of vacuoles in the cytoplasm proximal to the extruding nucleus. This finding led us to hypothesize that vesicle trafficking contributes to erythroblast enucleation.

Survivin is an IAP family member that plays an essential role in cellular proliferation as an essential component of the chromosome passenger complex. Survivin is highly expressed in embryos and in proliferating adult tissues, but it is not expressed in most differentiated cells. During tumorigenesis, however, survivin expression is dramatically upregulated. Although many studies have shown that survivin is required for cancer cells, the extent to which survivin contributes to the initiation of tumors is unknown. Here we show that transgenic mice that overexpress survivin in hematopoietic cells are at an increased risk of hematologic tumors. In examining how survivin might contribute to tumorigenesis, we observed that hematopoietic cells engineered to overexpress survivin are less susceptible to apoptosis. We conclude that survivin may promote tumorigenesis by imparting a survival advantage to cells that acquire additional genetic lesions.

Evidence is continuing to accumulate that the FMS-like tyrosine kinase 3 (FLT3) receptor plays an important role in acute leukemias. Acute myeloid leukemia patients often express constitutive active mutant forms of the receptor in their leukemic cells. A t(12;13)(p13;q12) translocation between Tel and the FLT3 receptor was recently described in a patient with myeloproliferative disease (MPD). Here a Tel-FLT3 construct mimicking this fusion protein was used to generate transgenic mice. The fusion protein was previously found to constitutively activate FLT3 signaling and transform Ba/F3 cells. Expression of the fusion protein in the transgenic mice was found in all tissues assayed including spleen, bone marrow (BM), thymus and liver. These mice developed splenomegaly and had a high incidence of MPD with extramedullary hematopoiesis in the liver and lymph nodes. Spleens also had increased dendritic and natural killer cell populations. In vitro analysis of the hematopoietic progenitor cells derived from Tel-FLT3 transgenic mice showed a significant increase in the number of CFU-GM in the BM, and CFU-GM, BFU-E and CFU-GEMM in the spleen. BM also showed significant increases of in vivo CFU-S colonies. Thus, transgenic mice expressing constitutively activated Tel-FLT3 develop MPD with a long latency and also result in the expansion of the hematopoietic stem/progenitor cells.

OBJECTIVE Produce prescriptions have shown promise in improving diabetes care, although most studies have used small samples or lacked controls. Our objective was to evaluate the impacts of a produce prescription program on glycemic control for patients with diabetes. RESEARCH DESIGN AND METHODS Participants included a nonrandom enrollment of 252 patients with diabetes who received a produce prescription and 534 similar controls from two clinics in Hartford, Connecticut. The start of the COVID-19 pandemic in March 2020 coincided with program implementation. Produce prescription enrollees received vouchers ($60 per month) for 6 months to purchase produce at grocery retail. Controls received usual care. The primary outcome was change in glycated hemoglobin (HbA1c) between treatment and control at 6 months. Secondary outcomes included 6-month changes in systolic (SBP) and diastolic blood pressure (DBP), BMI, hospitalizations, and emergency department admissions. Longitudinal generalized estimating equation models, weighted with propensity score overlap weights, assessed changes in outcomes over time. RESULTS At 6 months, there was no significant difference in change in HbA1c between treatment and control groups, with a difference of 0.13 percentage points (95% CI −0.05, 0.32). No significant difference was observed for change in SBP (3.85 mmHg; −0.12, 7.82), DBP (−0.82 mmHg; −2.42, 0.79), or BMI (−0.22 kg/m2; −1.83, 1.38). Incidence rate ratios for hospitalizations and emergency department visits were 0.54 (0.14, 1.95) and 0.53 (0.06, 4.72), respectively. CONCLUSIONS A 6-month produce prescription program for patients with diabetes, implemented during the onset of the COVID-19 pandemic, was not associated with improved glycemic control.