An aging mouse model of human chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is an age-dependent blood malignancy. Like many other age-dependent human diseases, laboratory animal research of CML uses young mice that do not factor in the influence of aging. To understand how aging may impact animal modeling of human age-dependent diseases, we established the first aging mouse model of human CML in BALB/c mice in the advanced age defined by 75% survival. This model was developed by noncytotoxic depletion of bone marrow lineage-positive cells followed by BCR-ABL retroviral transduction and transplantation. CML developed in aging mice shared many similarities to that in young mice, but had increased incidence of anemia that is often seen in human CML. Importantly, we showed that aging of both donor hematopoietic stem cells and recipient bone marrow niche impacted BCR-ABL mediated leukemogenesis and leukemia spectrum. Optimal CML induction relied on age-matching for donors and recipients, and cross-transplantation between young and old mice produced a mixture of different leukemia. Therefore, our model provides initial evidence of the feasibility and merit of CML modeling in aging mice and offers a new tool for future studies of CML stem cell drug resistance and therapeutic intervention in which aging would be taken into consideration as an influencing factor.

Systematic Review and Meta-Analysis of Sex-Specific COVID-19 Clinical Outcomes.

To successfully mitigate the extraordinary devastation caused by the Coronavirus disease 2019 (COVID-19) pandemic, it is crucial to identify important risk factors for this disease. One such neglected health determinant is the sex of the patient. This is an essential clinical characteristic, as it can factor into a patient's clinical management and preventative measures. Some clinical studies have shown disparities in the proportion between males and females that have more severe clinical outcomes or, subsequently, die from this disease. However, this association has not been unequivocally established. Thus, the purpose of this investigation was to examine the association between male sex and COVID-19 severity. We systematically reviewed the literature, identified studies that matched predetermined selection criteria, and performed a meta-analysis to evaluate the proportion of males among four disease severity categories. Appropriate assessment strategies were implemented to assess and minimize potential biases. The results of this meta-analysis indicated that males constituted a significantly higher proportion of those who had adverse clinical outcomes and died from COVID-19. As the coronavirus spread from the East to the West, male sex remained a consistent risk factor. Our results support the establishment of the male sex as an important risk factor for this disease. Early identification and appropriate medical care for males with lab-confirmed COVID-19 may substantially change the course of clinical prognosis, resulting in greater numbers of lives saved.

An emerging trend of rapid increase of leukemia but not all cancers in the aging population in the United States.

The "baby boomers" born in 1946-1964 in the United States (U.S.) started to reach the age of 65 in 2011, rapidly accelerating U.S. population aging. There are great public concerns about its impact on health care with anticipation of rising cancer incidences. We examined the incidences and deaths of leukemia and overall cancer in the U.S. from 1998 to 2018. The acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) incidences remained constant prior to 2011 but have climbed up substantially since then, and the chronic lymphocytic leukemia (CLL) incidence has increased continuously since 1998. The significant increase of myeloid leukemia and CLL incidences was strongly correlated with the U.S. population aging. The incidence of all cancers was increased in correlation with a small increase in aging population prior to 2011, but surprisingly has changed marginally since 2011, which was not significantly correlated with the accelerated population aging. We observed the most substantial decline of deaths with CML, whereas AML deaths continued to rise in the past 20 years. In conclusion, the overall cancer incidence was not increased as fast as previously feared with aging Americans; however, the incidences of myeloid leukemia and CLL significantly outpaced that of all cancers.