FYB1-targeted modulation of CAPG promotes AML progression.

Acute myeloid leukemia (AML) is a rare and heterogeneous disease. Over the past few decades, patient prognosis has improved with continuous improvements in treatment, but outcomes for some patients with primary drug resistance or relapse after treatment remain poor. Additional therapies to improve outcomes for these patients are urgently needed. FYB1 expression differs substantially between AML tissues and normal tissues. High FYB1 expression is correlated with poorer overall survival (OS), indicating that FYB1 may regulate AML progression. Therefore, understanding the effect of FYB1 on AML could improve the success rate of therapeutic approaches and prognosis for patients with AML. In this study, through analysis of large databases and both in vivo and in vitro experiments, we assessed the expression and role of FYB1 in AML and the relationship of FYB with patient prognosis. Downstream targets of the FYB1 gene were analyzed by RNA-seq. Database mining and in vitro experiments were used to further clarify the effect of the downstream target gelsolin-like actin-capping protein (CAPG) on AML cells and its relationship with patient prognosis. FYB1 expression was significantly higher in AML tissue and corresponded with a poor prognosis. FYB1 knockdown inhibited AML cell proliferation, promoted cell apoptosis, reduced cell adhesion capability and significantly reduced the tumor formation rate in mice. In addition, FYB1 knockdown induced a notable decrease in CAPG expression. The suppression of CAPG significantly inhibited cell proliferation and increased cell apoptosis. The conclusions of this study underscore the pivotal role of the FYB1/CAPG axis in promoting AML. We propose that the FYB1/CAPG axis could serve as a new thread in the development of therapeutic strategies for AML.

Mycobacterium abscessus pulmonary disease presenting with spontaneous pneumomediastinum and subcutaneous emphysema in childhood acute lymphoblastic leukemia: a case report and literature review.

INTRODUCTION: Mycobacterium abscessus is a rapidly growing mycobacterium commonly identified in adults with underlying pulmonary diseases but is rarely observed in children. A better understanding of this pathogen in children is essential. CASE PRESENTATION: We report the case of a 49-month-old female child without previous underlying pulmonary diseases but with acute lymphoblastic leukemia (ALL). The patient was complicated with pneumonia during chemotherapy, which was primarily characterized by spontaneous pneumomediastinum and subcutaneous emphysema on chest computed tomography (CT). M. abscessus sequences were detected by metagenomic next-generation sequencing in bronchoalveolar lavage fluid. With mechanical ventilation, closed thoracic drainage, and anti-infective therapy for 6 months, the patient's infection was controlled. The patient completed 2.5 years of treatment for ALL, and the drugs were discontinued. The patient currently remains in complete hematologic remission. DISCUSSION: We reviewed the literature on 33 children with M. abscessus pulmonary disease. These children mostly had underlying immunodeficiency. Chest CT most often showed nodular shadows, consolidation, and bronchiectasis. Spontaneous pneumomediastinum and subcutaneous emphysema were not reported as major manifestations. CONCLUSION: Spontaneous pneumomediastinum and subcutaneous emphysema were our patient's main characteristics on chest CT, and this study enriches the knowledge regarding possible imaging changes in M. abscessus pulmonary disease in children. This case report reflects good clinical experience in maintaining the balance between chemotherapy and anti-infective therapy in childhood ALL.

[Single Center Clinical Analysis of Bloodstream Infection Pathogens in Children with Acute Leukemia].

OBJECTIVE: To investigate the clinical features, distribution of pathogenic bacteria, and drug resistance of bloodstream infection in children with acute leukemia. METHODS: Clinical data of 93 blood culture-positive children with acute leukemia from January 2015 to December 2019 in Department of Pediatrics, The Second Hospital of Anhui Medical University were analyzed retrospectively. RESULTS: In these 93 cases, 78 cases were in the period of neutrophil deficiency. There were 54 Gram-negative bacteria (G-) (58.1%) found through blood culture, and the top 4 strains were Escherichia coli (15.1%), Klebsiella pneumoniae (13.9%), Pseudomonas aeruginosa (6.5%), and Enterobacter cloacae (6.5%). There were 39 Gram-positive bacteria (G+) (41.9%) detected, and the top 4 strains were Staphylococcus epidermidis (10.8%), Streptococcus pneumoniae (6.5%), Staphylococcus hemolyticus (5.4%), and Staphylococcus human (5.4%). Among 74 strains of pathogenic bacteria from acute lymphoblastic leukemia (ALL) children, there were 29 strains of G+ bacteria (39.2%) and 45 strains of G- bacteria (60.8%). While in 19 strains from acute myeloblastic leukemia (AML) patients, G- bacteria accounted for 47.4% and G+ bacteria accounted for 52.6%. In 15 ALL children without neutropenia, G+ bacteria made up the majority of the strains (66.7%). In the 93 strains of pathogenic bacteria, 13 (13.9%) strains were multidrug-resistant. Among them, extended-spectrum ß-lactamases accounted for 42.9%, carbapenemase-resistant enzyme Klebsiella pneumoniae 15.4%, and carbapenemase-resistant enzyme Enterobacter cloacae strains 33.3%, which were detected from G- bacteria. While, 13.3% of methicillin-resistant coagulase-negative Staphylococci accounted for 13.3% detected from G+ bacteria, but linezolid, vancomycin, teicoplanin Staphylococcus and Enterococcus resistant were not found. The average procalcitonin (PCT) value of G- bacteria infection was (11.02±20.282) ng/ml, while in G+ infection it was (1.81±4.911) ng/ml, the difference was statistically significant (P<0.05). The mean value of C-reactive protein (CRP) in G- infection was (76.33±69.946) mg/L, and that in G+ infection was (38.34±57.951) mg/L. The prognosis of active treatment was good, and only one case died of septic shock complicated with disseminated intravascular coagulation (DIC) and gastrointestinal bleeding caused by carbapenemase-resistant enzyme enterobacteriaceae. CONCLUSION: G- is the major bacteria in acute leukemia children with bloodstream infection, but the distribution of ALL and AML strains is different. G- bacteria dominates in ALL, while G+ bacteria and G- bacteria are equally distributed in AML. Non-agranulocytosis accompanied by bloodstream infections is dominant by G+ bacteria. The mean value of PCT and CRP are significantly higher in G- bacteria infection than in G+ bacteria.

Prognostic significance of steroid response in pediatric acute lymphoblastic leukemia: The CCCG-ALL-2015 study.

Introduction: Whether steroid response is an independent risk factor for acute lymphoblastic leukemia (ALL) is controversial. This study aimed to investigate the relationship between response to dexamethasone and prognosis in children with ALL. Methods: We analyzed the data of 5,161 children with ALL who received treatment in accordance with the Chinese Children's Cancer Group ALL-2015 protocol between January 1, 2015, and December 31, 2018, in China. All patients received dexamethasone for 4 days as upfront window therapy. Based on the peripheral lymphoblast count on day 5, these patients were classified into the dexamethasone good response (DGR) and dexamethasone poor response (DPR) groups. A peripheral lymphoblast count ≥1× 109/L indicated poor response to dexamethasone. Results: The age, white blood cell counts, prevalence of the BCR/ABL1 and TCF3/PBX1 fusion genes, and rates of recurrence in the central nervous system were higher in the DPR than in the DGR group (P<0.001). Compared to the DPR group, the DGR group had a lower recurrence rate (18.6% vs. 11%) and higher 6-year event-free survival (73% vs. 83%) and overall survival (86% vs. 92%) rates; nevertheless, subgroup analysis only showed significant difference in the intermediate-risk group (P<0.001). Discussion: Response to dexamethasone was associated with an early treatment response in our study. In the intermediate-risk group, dexamethasone response added a prognostic value in addition to minimal residual disease, which may direct early intervention to reduce the relapse rate.

Long-term follow-up of acute lymphoblastic leukemia in young children treated by the SCMC-ALL-2009 protocol.

This study evaluated the long-term therapeutic effect and prognostic factors of acute lymphoblastic leukemia (ALL) in 100 young Chinese children (<2 years old) who were enrolled in the Shanghai Children's Medical Center (SCMC)-ALL-2009 study in five pediatric hematological disease centers based on collaboration. The 5-year and 10-year event-free survivals (EFS) were 74.7 ± 3.2% and 73.3 ± 3.4%. The 10-year EFS rates for low risk, intermediate-risk, and high-risk patients were 81.9 ± 5.0%, 71.3 ± 4.3%, and 22.2 ± 13.9%, respectively. Relapse occurred in 19 patients. MRD results on day 55, good or poor response to prednisolone, and age at diagnosis were shown to have important prognostic and therapeutic implications. Compared with the SCMC-ALL-2005 protocol, showed that the 10-year-EFS and 10-year-overall survival of the SCMC-ALL-2009 protocol were better than that of the -2005 protocol. Notably, the intermediate-risk group was improved after the chemotherapy intensity was strengthened.

[Clinical Significance of Hepcidin in the Diagnosis of Infant Iron Deficiency Anemia].

OBJECTIVE: To explore the clinical diagnostic value and significance of hepciden level by detecting the expression of serum hepcidin before and after treatment of infant iron deficiency anemia (IDA) with or without vitamin D deficiency. METHODS: A total of 60 cases of infamt IDA were divided into A and B groups, the group A consisted of 20 IDA infants with vitamin D deficiency, group B consisted of 48 IDA infants without vitamin D deficiency and the control group included 26 healthy infants. Blood examination including HGB, MCV, MCH and MCHC was performed by hematological analyzer, the level of serum ferritin was assayed by chemiluminescence immunoassay, the levels of hepcidin and 25- (OH) D were assayed by ELISA. RESULTS: The levels of serum hepcidin in group A, B and control group before treatment were (29.16 ± 7.50), (27.11 ± 7.10) and (29.25 ± 8.39) ng/ml, respectively (P > 0.05). The level of serum hepcidin in group A and B after treatments was significantly higher than that in control group [ (36.21 ± 5.68) ng/ml vs (29.25 ± 8.39) ng/ml, P < 0.01; (34.16 ± 4.54) ng/ml vs (29.25 ± 8.39) ng/ml, P < 0.01]; but there were no significantly difference between group A and B (P > 0.05). The serum ferritin positively correlated with hepcidin in group B both before and after treatments (r = 0.352 and 0.367, P < 0.05, P < 0.05). CONCLUSION: The level of serum hepcidin has an important significance in poccess of evaluatng for therapeutic effect in infant iron deficiency anemia, but the interference effect of vitamin D deficience should be eliminated when the expression level of hepcidin is applicated for diagnosis and differential diagnosis.