Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center / 中华血液学杂志

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

Clinical and laboratory analysis of 17 patients with γδT-cell large granular lymphocyte leukemia / 中华血液学杂志

Objective: To compare the difference of the clinical and laboratory characteristics between γδ T-cell large granular lymphocyte leukemia (γδT-LGLL) and αβ T-cell large granular lymphocyte leukemia (αβT-LGLL) . Methods: The clinical and laboratory characteristics of 17 patients with γδT-LGLL and 91 patients with αβT-LGLL in the department of therapeutic center of anemia of enrolled in our hospital from January 2009 to January 2019 were retrospectively analyzed. Results: The median age of the 17 patients with γδT-LGLL was 54 years (range, 25-73 years) , the most common presenting symptom was anemia. In comparison with αβT-LGLL patients, splenomegaly was common (41% and 44%, respectively) , whereas hepatomegaly (12% and 5%, respectively) and lymphadenopathy (6% and 8%, respectively) were rare. The positive rates of antinuclear antibody (59% and 45%, respectively) were high, whereas the positive rates of rheumatoid factor (6% and 10%, respectively) were rare for both groups. There were no differences on peripheral blood counts between the two groups. However, γδT-LGLL patients were found to be predominantly expressed a CD4(-)/CD8(-) phenotype. Steroid therapy with prednisone was used alone as first-line therapy for 1 patient. Cyclosporin A (CsA) was used alone as first-line therapy for 3 patients. CsA in combination with steroids were administered in 13 patients. After 4 months treatment, 2 patients acquired complete response, 4 patients acquired partial response, the overall response was 35%. Conclusion: γδT-LGLL is a rare mature T-lymphocyte proliferative disease. Clinical and laboratory characteristics were quite similar for γδT-LGLL in compare with αβT-LGLL. γδT-LGLL predominantly expressed a CD4(-)/CD8(-) phenotype. The data presented here indicate the CsA is an effective option for the first-line treatment of γδT-LGLL.

Using target next-generation sequencing assay in diagnosing of 46 patients with suspected congenital anemias / 中华血液学杂志

Objective: To evaluate the impact of the targeted next-generation sequencing (NGS) assay for difficult congenital anemias. Methods: Blood Disease Hospital Anemia Panel 2014 (BDHAP-2014) including 217 known genes of congenital anemias was developed. NGS and parental verification were performed for patients who were suspected diagnosed with congenital anaemia from August 2014 to July 2017. Results: A total of 46 patients were enrolled in this study, the clinical suspection were 11 cases Fanconi anemia (FA), 8 cases congenital dyserythropoietic anemia (CDA), 6 cases congenital sideroblast anemia (CSA), 12 cases congenital hemolytic anemia (CHA), 1 case dyskeratosis congenital (DC), 4 cases iron-refractory iron deficiency anemia and 4 cases unexplained cytopenia (Uc), respectively. 28 (60.9%) of 46 patients became confirmed cases after targeted NGS, corresponding to 44 mutations of which 33 were new. 26(56.5%) patients with results of the assay matching to clinical suspection, including FA (5/11, 45.5%), CSA (6/6, 100.0%), CDA (3/8, 37.5%) and CHA (12/12, 100.0%). 2 (4.3%) cases not matching to clinical suspection, including dyskeratosis congenital (DC) was made in 1(2.2%) patients with suspected FA and familial hemophagocytic lymphohistiocytosis (FHL) was made in 1(2.2%) patients with suspected unexplained cytopenia (Uc). In 12 CHA patients, the hemolytic type was further clarified by the NGS. The remaining 18 cases were not clearly diagnosed. Conclusion: Targeted NGS assay is of major impact on congenital anemias. The assay should be used routinely in congenital anemias.

The relationship between insulin resistance and glucocorticoids in patients with systemic lupus erythematosus / 天津医药

Objective To evaluate insulin resistance (IR) in patients with systemic lupus erythematosus (SLE) and investigate the effect of glucocorticoids on IR and its clinical significance. Methods Three hundred and one SLE patients and 103 healthy volunteers hospitalized in our hospital from May 2013 to May 2017 were included in this study. Homeostasis model assessment (HOMA) was used to calculate insulin resistance index (HOMA-IR), HOMA-βcell function index (HBCI) and insulin sensitivity index (ISI). The IR grouping was determined by using the upper 1/4 of the HOMA-IR index of 103 healthy volunteers as the cut point. According to the dose of glucocorticoids in the last 3 months, the SLE group was divided into glucocorticoids>7.5 mg/d group,≤7.5 mg/d group and without glucocorticoids group. These parameters were compared with all groups respectively. Furthermore, related factors for HOMA-IR were analyzed by linear correlation. Results Compared with control group, triacylglycerol (TG, P<0.01), fasting insulin (FINS, P<0.01), HOMA-IR (P<0.01), HOMA-HBCI (P<0.05) were significantly increased and high-density lipoprotein cholesterol (HDL-C, P<0.01) and ISI (P<0.01) were significantly lower in SLE group. However, there were no significant differences in TG, FINS, HOMA-IR and ISI between different doses of glucocorticoid groups (P>0.05). The level of HOMA-HBCI was significantly higher in two groups with glucocorticoids than that without glucocorticoid group and normal control group (P<0.05), while there was no significant difference in HOMA-HBCI between without glucocorticoid group and the normal control group ( P>0.05). HOMA-IR was positively correlated with fasting blood glucose (FBG, r=0.566, P<0.01), FINS (r=0.949, P<0.01) and HOMA-HBCI (r=0.280, P<0.01). But there was a negative correlation between TG (r=-0.139, P<0.01) and ISI (r=-0.896, P<0.01). Conclusion Insulin secretion is abnormal and the incidence of IR is elevated in SLE patients. Long term glucocorticoid therapy may be involved in the formation of IR.