Despite major therapeutic advances in the treatment of acute lymphoblastic leukemia (ALL), resistances and long-term toxicities still pose significant challenges. Cyclins and their associated cyclin-dependent kinases are one focus of cancer research when looking for targeted therapies. We discovered cyclin C to be a key factor for B-cell ALL (B-ALL) development and maintenance. While cyclin C is not essential for normal hematopoiesis, CcncΔ/Δ BCR::ABL1 + B-ALL cells fail to elicit leukemia in mice. RNA sequencing experiments revealed a p53 pathway deregulation in CcncΔ/Δ BCR::ABL1 + cells resulting in the inability of the leukemic cells to adequately respond to stress. A genome-wide CRISPR/Cas9 loss-of-function screen supplemented with additional knock-outs unveiled a dependency of human B-lymphoid cell lines on CCNC. High cyclin C levels in B-cell precursor (BCP) ALL patients were associated with poor event-free survival and increased risk of early disease recurrence after remission. Our findings highlight cyclin C as a potential therapeutic target for B-ALL, particularly to enhance cancer cell sensitivity to stress and chemotherapy.

The Philadelphia (Ph) chromosome, a product of the reciprocal translocation t(9;22)(q34;q11) between chromosomes 9 and 22, encodes the BCR::ABL1 fusion oncoprotein.¹ The constitutively active BCR::ABL1 tyrosine kinase is a hallmark of chronic myeloid leukemia (CML) and drives a subset of acute lymphoblastic leukemia (ALL). The incidence of Ph positive (Ph⁺) ALL correlates with age, from only 3% in pediatric ALL to around 25% in older adults.² Direct targeting of the BCR::ABL1 kinase with tyrosine kinase inhibitors (TKI) has been a breakthrough in targeted cancer therapy. Despite efforts to counteract TKI resistance and improve safety profiles, refractory BCR::ABL1⁺ leukemia, as well as toxicities and long-term side effects of TKI, present particular therapeutic challenges.^3–5

The clinical relevance of cyclins and their associated cyclin-dependent kinases (CDK) has been a major focus of research for several years. Cyclin-CDK complexes do not only drive the cell cycle, but are also important players in various other cellular processes including transcriptional and epigenetic regulation, metabolism or stem cell self-renewal.⁶ In line with their importance in different pathways, cyclin-CDK complex dysregulation is implicated in many different types of cancer.⁷

A new study has unveiled when chronic myeloid leukaemia, a type of cancer that affects the blood and bone marrow, arises in life and how fast it grows. Researchers reveal explosive growth rates of cancerous cells years before diagnosis and variation in these rates of growth between patients. Such rapid growth rates had previously not been observed in most other cancers.

Researchers used whole genome sequencing to study when BCR::ABL1 – an abnormal fusion of the different genes called BCR and ABL1, which is known to cause chronic myeloid leukaemia. The team investigated when BCR::ABL1 first arises in a blood cell and how quickly these cells with this genetic change then multiply and expand to lead to a diagnosis of a type of leukaemia.

The research, published in Nature, contributes to the scientific understanding of how strong this abnormal fusion gene is in its ability to drive cancer.

Northwestern Medicine investigators have discovered how disruptions in the circadian rhythm in our muscles combined with poor diet can contribute to the development of diabetes, according to a recent study published in Proceedings of the National Academy of Sciences.

“When we mess up our circadian rhythms through environmental circadian disruption like shift work, jet lag or sleep deprivation, it’s possible that it’s impacting our muscle clocks and metabolism. If that’s happening and we are combining this with an unhealthy diet, this might make it more likely for us to develop glucose intolerance and diabetes,” said Clara Peek, Ph.D., assistant professor of Biochemistry and Molecular Genetics and of Medicine in the Division of Endocrinology, Metabolism and Molecular Medicine, who was senior author of the study.

The body’s natural circadian clock is comprised of proteins called transcription factors that are present throughout the body, including muscle tissue. The clock synchronizes physical and behavioral changes to the external environment during the 24-hour light cycle.

Alpha-1-antitrypsin is a so-called protease inhibitor, a type of enzyme inhibitor. It is produced in the liver but exerts its effects in the lungs, where it regulates immune cell activity. This regulation is crucial, and an overactive immune response can cause serious lung diseases.

However, some individuals carry a genetic mutation that causes the alpha-1 protein to fold incorrectly. As a result, too little functional alpha-1 is produced, and insufficient amounts reach the lungs.

The mutation is inherited from one or both parents. About 1 in 20 people in Europe carry the heterozygous form of the mutation—inherited from only one parent—and often experience no symptoms or only mild ones. In contrast, the rarer homozygous form, inherited from both parents, affects approximately 1 in 2000 individuals and is much more severe.