Circular RNAs (circRNAs) are single-stranded RNAs that have received much attention in recent years. CircRNAs lack a 5\' head and a 3\' poly-A tail. The structure of this type of RNAs make them resistant to digestion by exonucleases. CircRNAs are expressed in different cells and have various functions. The function of circRNAs is done by sponging miRNAs, changing gene expression, and protein production. The expression of circRNAs changes in different types of cancers, which causes changes in cell growth, proliferation, differentiation, and apoptosis. Changes in the expression of circRNAs can cause the invasion and progression of tumors. Studies have shown that changes in the expression of circRNAs can be seen in acute lymphoid leukemia (ALL) and chronic lymphoid leukemia (CLL). The conducted studies aim to identify circRNAs whose expression has changed in these leukemias and their more precise function so that these circRNAs can be identified as biomarkers, prediction of patient prognosis, and treatment targets for ALL and CLL patients. In this study, we review the studies conducted on the role and function of circRNAs in ALL and CLL patients. The results of the studies show that there is a possibility of using circRNAs as biomarkers in the identification and treatment of patients in the future.

BACKGROUND: Acute leukemia is the most common pediatric cancer, with an incidence peak at 2-5 years of age. Despite the medical advances improving survival rates, children suffer from significant side effects of treatments as well as its high social and economic impact. The frequent prenatal origin of this developmental disease follows the two-hit carcinogenesis model established in the 70s: a first hit in prenatal life with the creation of genetic fusion lesions or aneuploidy in hematopoietic progenitor/stem cells, and usually a second hit in the pediatric age that converts the preleukemic clone into clinical leukemia. Previous research has mostly focused on postnatal environmental factors triggering the second hit.
CONCLUSIONS: There is scarce evidence on prenatal risk factors associated with the first hit. Mainly retrospective case-control studies suggested several environmental and lifestyle determinants as risk factors. If these associations could be confirmed, interventions focused on modifying prenatal factors might influence the subsequent risk of leukemia during childhood and reveal unexplored research avenues for the future. In this review, we aim to comprehensively summarize the currently available evidence on prenatal risk factors for the development of childhood leukemia. According to the findings of this review, parental age, ethnicity, maternal diet, folate intake, alcohol consumption, X-ray exposure, pesticides, perinatal infections, and fetal growth may have a significant role in the appearance of preleukemic lesions during fetal life. Other factors such as socioeconomic status, consumption of caffeinated beverages, and smoking consumption have been suggested with inconclusive evidence. Additionally, investigating the association between prenatal factors and genetic lesions associated with childhood leukemia at birth is crucial. Prospective studies evaluating the link between lifestyle factors and genetic alterations could provide indirect evidence supporting new research avenues for leukemia prevention. Maternal diet and lifestyle factors are modifiable determinants associated with adverse perinatal outcomes that could be also related to preleukemic lesions.
CONCLUSIONS: Parental age, ethnicity, maternal diet, folate intake, alcohol consumption, X-ray exposure, pesticides, perinatal infections, and fetal growth may have a significant role in the appearance of preleukemic lesions during fetal life. Dedicating efforts to studying maternal lifestyle during pregnancy and its association with genetic lesions leading to childhood leukemia could lead to novel prevention strategies.

The ABO system is an essential blood group in clinical transfusion medicine implicated in several human diseases. The ABO system has been investigated for over a century, with various studies exploring potential links to disease susceptibility. The study examines the possible relationship between leukemia and the distribution and the ABO blood group system discrepancy. A comprehensive review was conducted on the recommended databases to review the ABO blood groups, their association with leukemia, and the expected changes in blood groups among leukemia patients. The study highlights different kinds of leukemia, such as acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL), their characteristics, and their relationship with ABO blood groups. The document concludes that studying ABO blood group distributions among leukemia patients showed that the most common blood group in acute leukemia is the A group, while in chronic leukemia, the O group is predominant; more studies are required. This study also confirmed an association between leukemia and ABO blood group discrepancy.

OBJECTIVE: Acute lymphoblastic leukemia (ALL) is a type of blood cancer that affects white blood cells. Here, we use data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, to estimate the burden and incidence rate changes in adolescents and young adults (AYA) ALL in the Western Pacific Region and to reveal potential risk factors of incidence- and mortality rates.
METHODS: The GBD 2019 study data was stratified by sex, age, country, and territory. We calculated the Estimated annual percentage changes (estimated APC) in mortality and incidence rates for each of the 25 countries and territories of the western Pacific region from 1990 to 2019.
RESULTS: This study found global AYA ALL incidence rates had increased while the mortality rates had decreased between 1990 and 2019. Moreover, healthcare access and quality (HAQ), and government per capita health spending were identified as country-level risk factors of AYA ALL incidence rates, while HAQ, male education, and sex were identified as mortality rate predictors in 25 Western Pacific Region countries.
CONCLUSIONS: To address and reduce the burden of incidence and mortality among AYA, various regions around the world, particularly developing countries, could revise their AYA prevention and treatment strategies.

Treatment of refractory and relapsed (R/R) B acute lymphoblastic leukemia (B-ALL) is an unmet medical need in both children and adults. Studies carried out in the last two decades have shown that autologous T cells engineered to express a chimeric antigen receptor (CAR-T) represent an effective technique for treating these patients. Antigens expressed on B-cells, such as CD19, CD20, and CD22, represent targets suitable for treating patients with R/R B-ALL. CD19 CAR-T cells induce a high rate (80-90%) of complete remissions in both pediatric and adult R/R B-ALL patients. However, despite this impressive rate of responses, about half of responding patients relapse within 1-2 years after CAR-T cell therapy. Allo-HSCT after CAR-T cell therapy might consolidate the therapeutic efficacy of CAR-T and increase long-term outcomes; however, not all the studies that have adopted allo-HSCT as a consolidative treatment strategy have shown a benefit deriving from transplantation. For B-ALL patients who relapse early after allo-HSCT or those with insufficient T-cell numbers for an autologous approach, using T cells from the original stem cell donor offers the opportunity for the successful generation of CAR-T cells and for an effective therapeutic approach. Finally, recent studies have introduced allogeneic CAR-T cells generated from healthy donors or unmatched, which are opportunely manipulated with gene editing to reduce the risk of immunological incompatibility, with promising therapeutic effects.

Acute leukemias (AL) are aggressive neoplasms with high mortality rates. Metabolomics and oxidative status have emerged as important tools to identify new biomarkers with clinical utility. To identify the metabolic differences between healthy individuals (HI) and patients with AL, a multiplatform untargeted metabolomic and lipidomic approach was conducted using liquid and gas chromatography coupled with quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS or GC-QTOF-MS). Additionally, the total antioxidant capacity (TAC) was measured. A total of 20 peripheral blood plasma samples were obtained from patients with AL and 18 samples from HI. Our analysis revealed 135 differentially altered metabolites in the patients belonging to 12 chemical classes; likewise, the metabolic pathways of glycerolipids and sphingolipids were the most affected in the patients. A decrease in the TAC of the patients with respect to the HI was evident. This study conducted with a cohort of Colombian patients is consistent with observations from other research studies that suggest dysregulation of lipid compounds. Furthermore, metabolic differences between patients and HI appear to be independent of lifestyle, race, or geographic location, providing valuable information for future advancements in understanding the disease and developing more global therapies.

Leukemia is a type of cancer that affects the blood and bone marrow. Acute lymphoid leukaemia, also known as ALL, is regarded as one of the deadliest forms of cancer. Due to the rapid increase in various cancer cases and the development of resistance in cancer cells, it is necessary to identify novel lead molecules with more potent anticancer properties. There is a growing interest in using herbal products/analogs as multi-component agents (as anticancer agents and immunomodulators) for cancer treatment. In the present investigation, an attempt has been made to explore the anticancer and immunomodulatory activity of P19, an analog of parthenin in ALL. P19 was reported to exhibit anticancer efficacy by triggering apoptotic signaling events in human leukaemia HL-60 cells by significant NO production. In contrast to this finding, ROS and NO were not required for P19-mediated apoptosis in Raji cells. The mechanism of action of P19 was observed to be cancer cell lineage dependent. P19 demonstrated very effective anticancer properties against ALL (IC50 3µM). Molecular investigations revealed that P19 induced mitochondrion mediated apoptosis by Bax localization to mitochondria and enhanced cytosolic calcium in the cytoplasm. Further activation of the caspase 3, caspase 8 and PARP cleavage suggested the involvement of the caspase-mediated apoptosis. Anti-proliferative activity revealed the telomerase inhibition and cell cycle arrest in G0/G1 phase after P19 treatment. Immunomodulatory effects of the P19 revealed the enhanced INFɣ and NO production in Jurkat and THP cells. Owing to its antiproliferative and immunomodulatory potential against leukemia cells P19 can further be explored as effective therapeutics against leukemia.

UNASSIGNED: The clarification of etiopathology, the improvement of chemotherapy regimens and their risk stratifications, and the improvement in treatment support have increased the survival of children and adolescents affected by Acute Lymphoblastic Leukemia (ALL) past few years. This study aimed to estimate overall survival (OS) and event-free survival (EFS) in an onco-hematology treatment center in Brazil, reports the main clinical-laboratory characteristics of patients at diagnosis, verify the frequency of treatment-related adverse effects and the main causes of death.
UNASSIGNED: Retrospective analysis involving patients diagnosed with ALL, treated with the protocol of the Brazilian Group for Treatment of Leukemias in Childhood (GBTLI), between 2010 and 2020 was carried out; the outcomes (relapse, deaths, development of new neoplasms) were analyzed SPSS® software was used for the statistical analyses, and the p-value was considered significant when less than 0.05 for all analyses.
UNASSIGNED: 109 patients were included in the study; the median age was 5 years, with a slight predominance of males. Sixty-six patients were classified as high-risk (HR) group and 43 patients were classified as low-risk (LR) group. After 5 years of diagnosis, the OS was 71.5%, and the EFS was 65%. No statistical difference was found between the HR and LR groups for OS and EFS, while leukocyte counts were statistically associated with the outcome of death (p = 0.028). Among the patients, 28 (25.6%) died due to infection accounting 46.4% of death causes. Among the 34 patients with unfavorable outcomes (death and/or relapse), 32 had no research for the minimal residual disease at the end of remission induction, and 25 were not investigated for the presence of chromosomal abnormalities. The most reported complications and treatment-related adverse effects were increased liver transaminases (85.9%), airway infection (79.4%), oral mucositis (67.2%), febrile neutropenia (64.4%), and diarrhea (36.4%).
UNASSIGNED: The rates of OS and EFS obtained in this cohort are similar to those obtained in the few previous similar studies in Brazil and lower than those carried out in developed countries. The unavailability of prognostic tests may have hindered risk stratification and influenced the results obtained.

UNASSIGNED: China has experienced one of the fastest increases in the incidence of acute lymphoid leukemia (ALL). The aim of this study was to assess the long-term trends of the incidence and mortality of ALL in mainland China between 1990 and 2019 and to project these trends through 2028.
UNASSIGNED: Data on ALL were extracted from the Global Burden of Disease Study 2019; population data were extracted from World Population Prospects 2019. An age-period-cohort framework was used in the analysis.
UNASSIGNED: The net drift for the incidence of ALL was 7.5% (95% confidence interval [CI]: 7.1%, 7.8%) per year in women and 7.1% (95% CI: 6.7%, 7.6%) in men, and local drift was found to be higher than 0 in every studied age group (p<0.05). The net drift for mortality was 1.2% (95% CI: 1.0%, 1.5%) in women and 2.0% (95% CI: 1.7%, 2.3%) in men. Local drift was lower than 0 in boys aged 0-4 years and girls aged 0-9 years and higher than 0 in men aged 10-84 years and women aged 15-84 years. The estimated period relative risks (RRs) for both incidence and mortality showed increasing trends in the recent period. The cohort RRs for incidence showed increasing trends in both sexes; however, the cohort RR for mortality was decreased in the recent birth cohort (women born after 1988-1992 and men born after 2003-2007). Compared with that in 2019, the incidence of ALL in 2028 is projected to increase by 64.1% in men and 75.0% in women, and the mortality is predicted to decrease by 11.1% in men and 14.3% in women. The proportion of older adult/adults individuals with incident ALL and ALL-related death was projected to increase.
UNASSIGNED: Over the last three decades, the incidence and mortality rates of ALL have generally increased. It is projected that the incidence rate of ALL in mainland China will continue to increase in the future, but the associated mortality rate will decline. The proportion of older adult/adults individuals with incident ALL and ALL-related death was projected to increase gradually among both sexes. More efforts are needed, especially for older adult/adults individuals.

Acute lymphoblastic leukemia (ALL) is a hematological cancer that can cause ocular tissue involvement. Asparaginase is a chemotherapy regimen that is commonly used in leukemia which could lead to similar ocular manifestations. We report a patient with a history of ALL for seven months on asparaginase therapy and persistent cerebral sinus venous thrombosis (CSVT) with acute venous infarction in the left frontal lobe presented with worsening vision. On examination, he had a visual acuity (VA) of (6/21) in the right eye and (6/60) in the left eye, with a mild left eye abduction limitation. Fundal examination showed bilateral prominent multilayered retinal hemorrhages and papilledema with absence of leukemic infiltration. His chemotherapy regimen was held and a one month follow up was scheduled. Follow up after one month of chemotherapy cessation showed resolution of both VA and fundal exam findings. It is crucial to differentiate between asparaginase toxicity and infiltration of the disease in ALL patients. As this would determine whether the treatment should be continued or suspended.