CDKN2A deletions are associated with poor outcomes in 101 adults with T-cell acute lymphoblastic leukemia.

The identification of genetic risk subgroups of T-cell acute lymphoblastic leukemia (T-ALL) may provide evidence for risk stratification and individualized treatment. We investigated the characteristics and prognostic value of tumor suppressor gene CDKN2A deletions in 101 patients with T-ALL. The CDKN2A deletion was present in 23% (23/101) of T-ALL by fluorescence in situ hybridization (FISH). The most common type of CDKN2A deletion was homozygous deletion (70%, 16/23). A lower frequency of CDKN2A deletion was found in patients with early T-cell precursor (ETP) ALL than in patients with non-ETP-ALL (10.4% vs 34.0%; P = .008). Deletion of CDKN2A was significantly associated with younger age (P = .001), higher white blood cell (WBC) count (P < .001) and higher lactate dehydrogenase (LDH) level (P = .002). Patients with CDKN2A deletion had lower 2-year overall survival (OS) and event-free survival (EFS) rates than patients without CDKN2A deletion (2-year OS: 18.6% ± 8.9% vs 47.4% ± 6.2%, P = .032; EFS: 16.4 ± 8.3 vs 38.6 ± 5.9%, P = .022). In multivariable analysis, CDKN2A deletion was an independent adverse prognostic factor for OS (P = .016). In conclusion, adult T-ALL patients with CDKN2A deletion had a poor prognosis, and these patients might benefit from intensive chemotherapy or allogeneic hematopoietic stem-cell transplantation.

Comparison of Early T-Cell Precursor and Non-ETP Subtypes Among 122 Chinese Adults With Acute Lymphoblastic Leukemia.

Background: Adult T-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy and significantly linked to poor outcomes. Early T-cell precursor (ETP) leukemia is a unique subtype of T-ALL. The aim of this study is to compare the differences between ETP and non-ETP ALLs in China. Methods: We retrospectively analyzed the records of 122 adult T-ALL patients diagnosed and treated at our center between January 2014 and June 2019. All the patients enrolled were categorized into ETP and non-ETP ALL by immunophenotype, and further statistical analyses about clinical data and prognostic factors were performed. Results: Among the 122 cases, the male-to-female ratio was 2.8:1, and the median age is 29 (range, 16-82) years. Except for 10 patients with insufficient immunophenotyping results, 47.3% (53/112) are ETP and 52.7% (59/112) are non-ETP. Compared with non-ETP patients, ETP-ALL patients had lower white blood cell counts and lactate dehydrogenase levels, while they were older and had higher platelet counts and fibrinogen levels (all p < 0.05). Complete remission (CR) was achieved in 68.0% (83/122) of patients, 64.2 and 76.3% in ETP and non-ETP, respectively (p = 0.160). In total, 44.6% (37/83) of patients relapsed. Allogeneic stem cell transplantation (allo-SCT) was successfully performed in 36.1% (44/122) of patients, of which 79.5% (35/44) were in CR1. With a median follow-up of 9.1 (range, 0.5-70.3) months, the estimated 2-year overall survival (OS) and relapse-free survival (RFS) rates for the cohort were 38.0 ± 5.1 and 39.1 ± 6.3%, respectively. In the ETP group, the 2-year OS rate was 40.7 ± 8.2% and the RFS rate was 47.2 ± 10.7%, while in the non-ETP group, the 2-year OS rate was 37.9 ± 7.0% and the RFS rate was 39.2 ± 8.3% (both p > 0.05). In the landmark analysis of CR1 patients who had a survival of more than 6 months, the allo-SCT group had significantly better survival outcomes than the chemotherapy group, and the 2-year OS rates and RFS rates were 80.1 ± 7.3 vs. 28.4 ± 8.4% and 68.9 ± 8.8 vs. 12.8 ± 7.2%, respectively (both p < 0.0001). A multivariate analysis suggests that allo-SCT acts as an independent prognostic factor for both OS and RFS. Conclusions: Our results revealed that ETP accounted for a high proportion of T-ALL in Chinese. There are no CR rates and prognosis differences between ETP and non-ETP. Allo-SCT in CR1 can significantly improve patients' survival.

Characteristics of chemotherapy-induced diabetes mellitus in acute lymphoblastic leukemia patients.

Acute lymphocytic leukemia (ALL) is one of the most common malignancies, especially in young people. Combination chemotherapy for ALL typically includes corticosteroids (Kantarjian et al., 2000). Hyperglycemia is a well-recognized complication of corticosteroids, and chemotherapy-induced diabetes (CID) is not uncommon (27.5%-37.0%) during the treatment of ALL (Hsu et al., 2002; Weiser et al., 2004; Alves et al., 2007). Besides the effect of corticosteroids, potential factors triggering hyperglycemia in ALL also include direct infiltration of the pancreas by leukemia cells and ß cell dysfunction induced by chemotherapeutic agents such as L-asparagine (Mohn et al., 2004).

Construction of an efficient genomic editing system with CRISPR/Cas9 in the vector mosquito Aedes albopictus.

Aedes (Stegomyia) albopictus, also known as the Asian tiger mosquito, is a mosquito which originated in Asia. In recent years, it has become increasingly rampant throughout the world. This mosquito can transmit several arboviruses, including dengue, Zika and chikungunya viruses, and is considered a public health threat. Despite the urgent need of genome engineering to analyze specific gene functions, progress in genetical manipulation of Ae. albopictus has been slow due to a lack of efficient methods and genetic markers. In the present study, we established targeted disruptions in two genes, kynurenine hydroxylase (kh) and dopachrome conversion enzyme (yellow), to analyze the feasibility of generating visible phenotypes with genome editing by the clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated protein 9 (Cas9) system in Ae. albopictus. Following Cas9 single guide RNA ribonucleoprotein injection into the posterior end of pre-blastoderm embryos, 30%-50% of fertile survivors produced alleles that failed to complement existing kh and yellow mutations. Complete eye and body pigmentation defects were readily observed in G1 pupae and adults, indicating successful generation of highly heritable mutations. We conclude that the CRISPR/Cas9-mediated gene editing system can be used in Ae. albopictus and that it can be adopted as an efficient tool for genome-scale analysis and biological study.