OBJECTIVE: To explore the clinical and laboratory characteristics of hematological tumors with different types of abnormalities in platelet derived growth factor β (PDGFRβ) gene. METHODS: A retrospective analysis was carried out on 141 patients with abnormal long arm of chromosome 5 (5q) and comprehensive medical history data from Changhai Hospital Affiliated to Naval Medical University from 2009 to 2020, and their clinical data were collected. R-banding technique was used for chromosomal karyotyping analysis for the patient's bone marrow, and fluorescence in situ hybridization (FISH) was used to detect the PDGFRβ gene. The results of detection were divided into the amplification group, deletion group, and translocation group based on FISH signals. The three sets of data column crosstabs were statistically analyzed, and if the sample size was n >= 40 and the expected frequency T for each cell was >= 5, a Pearson test was used to compare the three groups of data. If N < 40 and any of the expected frequency T for each cell was < 5, a Fisher's exact test is used. Should there be a difference in the comparison results between the three sets of data, a Bonferroni method was further used to compare the data. RESULTS: In total 98 patients were detected to have PDGFRβ gene abnormalities with the PDGFRβ probe, which yielded a detection rate of 69.50% (98/141). Among these, 38 cases (38.78%) had PDGFRβ gene amplifications, 57 cases (58.16%) had deletions, and 3 (3.06%) had translocations. Among the 98 cases, 93 were found to have complex karyotypes, including 37 cases from the amplification group (97.37%, 37/38), 55 cases from the deletion group (96.49%, 55/57), and 1 case from the translocation group (33.33%, 1/3). Analysis of three sets of clinical data showed no significant gender preponderance in the groups (P > 0.05). The PDGFRβ deletion group was mainly associated with myeloid tumors, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (P < 0.001). The PDGFRβ amplification group was more common in lymphoid tumors, such as multiple myeloma (MM) (P < 0.001). The PDGFRβ translocation group was also more common in myelodysplastic/myeloproliferative tumors (MDS/MPN). CONCLUSION Tumors with PDGFRβ gene rearrangement may exhibit excessive proliferation of myeloproliferative tumors (MPN) and pathological hematopoietic changes in the MDS, and have typical clinical and hematological characteristics. As a relatively rare type of hematological tumor, in addition to previously described myeloid tumors such as MPN or MDS/MPN, it may also cover lymphoid/plasma cell tumors such as multiple myeloma and non-Hodgkin's lymphoma.
Humans ; Clinical Relevance ; Hematologic Neoplasms/genetics* ; In Situ Hybridization, Fluorescence ; Multiple Myeloma ; Myelodysplastic Syndromes ; Retrospective Studies ; Translocation, Genetic

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.
Humans ; Aged ; Middle Aged ; Leukemia, Myelomonocytic, Chronic/genetics* ; Prognosis ; Splicing Factor U2AF/genetics* ; Mutation ; Myelodysplastic Syndromes/genetics* ; Leukemia, Myeloid, Acute/genetics*

Humans ; Hematopoietic Stem Cell Transplantation ; Myelodysplastic Syndromes/therapy* ; Nuclear Proteins/genetics* ; Transplantation Conditioning

OBJECTIVE: To assess the value of fluorescence in situ hybridization (FISH) technique for the verification of the clonalities of non-clonal cytogenetic abnormalities (n-CCA) identified by conventional chromosome banding analysis (CBA) in patients with Myelodysplastic syndrome (MDS). METHODS: Clinical data and results of karyotyping and FISH assays for 91 patients of MDS with n-CCA identified by CBA were retrospectively analyzed. In total 94 non-clonal +8, 5q-, -7/7q- or 20q- were detected by CBA, among which 43 (45.7%) were verified to be clonal abnormalities by FISH. RESULTS: The detection rates for +8, 5q-, -7/7q- and 20q- by FISH were 47.6% (30/63), 25% (2/8), 41.7% (5/12), 40% (2/5) and 66.7% (4/6), respectively, with the positive cells accounting for 4% to 90% of all counted cells, with a median value of 7%. The 91 patients were divided into three groups including ≥ 20, 10 ~< 20 and < 10 based on the numbers of metaphase cells in CBA, and the detection rates by FISH for the three groups were 43.7% (31/71), 33.3% (3/9) and 63.6% (7/11), respectively, which showed no statistically difference (P > 0.05). Continuous CBA and FISH surveys were conducted for 26 patients who received supportive treatment, and the results revealed that 91.7% (11/12) of FISH-verified positive abnormalities had persisted, whereas 92.9% (13/14) of the n-CCA verified as negative by FISH was transient. CONCLUSION Nearly half of the CBA identified n-CCA have been verified as clonal aberrations by FISH, and the FISH detection rate showed no correlation with the number of metaphase cells. FISH test is strongly recommended for verifying the clonalities of n-CCA detected by CBA, and continuous cytogenetic survey of the patients with MDS is necessary.
Humans ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Chromosome Aberrations ; Karyotyping ; Myelodysplastic Syndromes/genetics*

Humans ; Philadelphia Chromosome ; Neoplasms ; Myelodysplastic Syndromes/genetics* ; Disease Progression

Humans ; Ulcer ; Intestinal Diseases ; Myelodysplastic Syndromes/genetics* ; Trisomy/genetics* ; Behcet Syndrome

Objective: To exploring the clinical features of SF3B1-mutated myelodysplastic syndrome with excess blasts (MDS-EB) and analyzing the association between SF3B1 mutation, and efficacy and prognostic significance for patients with MDS-EB. Methods: This was a retrospective case series study. The clinical data of 266 patients with MDS-EB diagnosed in the First Affiliated Hospital of Zhengzhou University between April 2016 and November 2021 were analyzed. The observed indicators included blood routine counts, mutated genes, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and leukemia-free survival (LFS). The Kaplan-Meier method was used to depict the survival curves. The Log-rank test method was equally used to compare survival across groups and performed the Cox proportional hazard regression model for prognostic analysis. Results: In 266 patients with MDS-EB, 166 (62.4%) were men, and the median age was 57 (17-81) years. Moreover, there were included 26 and 240 patients in the SF3B1-mutated and SF3B1 wild-type groups. Patients in the SF3B1-mutated group were older [median age 65 (51, 69) years vs. 56 (46, 66) years, P=0.033], had higher white blood cell (WBC) counts [3.08 (2.35, 4.78) × 10⁹/L vs. 2.13 (1.40, 3.77) × 10⁹/L], platelet (PLT) counts [122.5 (50.5, 215.0) ×10⁹/L vs. 49.0 (24.3, 100.8) × 10⁹/L], absolute neutrophil counts (ANC) [1.83 (1.01, 2.88) × 10⁹/L vs. 0.80 (0.41, 1.99) × 10⁹/L]and occurrence of DNMT3A mutation [23.1% (6/26) vs. 6.7% (16/240)] (all P<0.05). The ORR were similar in both groups after 2 and 4 cycles of therapy (P=0.348, P=1.000). Moreover, the LFS (P=0.218), PFS (P=0.179) and OS (P=0.188) were similar across the groups. Univariate Cox analysis revealed that SF3B1 mutation did not affect the prognosis of patients with MDS-EB (OS: P=0.193; PFS: P=0.184). Conclusions: Patients with SF3B1 mutation were older, with greater WBC, PLT, and ANC, and SF3B1 mutation easily co-occurred with DNMT3A mutation. From this model, there were no significant differences in efficacy and survival of MDS-EB with or without SF3B1 mutation.
Aged ; Female ; Humans ; Male ; Middle Aged ; Leukocytes ; Mutation ; Myelodysplastic Syndromes/diagnosis* ; Phosphoproteins/genetics* ; Prognosis ; Retrospective Studies ; RNA Splicing Factors/genetics* ; Adolescent ; Young Adult ; Adult ; Aged, 80 and over

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As₄S₄) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.
Arsenicals/therapeutic use* ; DNA ; DNA Methylation/genetics* ; Humans ; Myelodysplastic Syndromes/genetics* ; Sulfides

OBJECTIVE: To investigate the genetic and prognostic characteristics of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) patients. METHODS: There were 230 non-M3 AML patients treated in Ningbo First Hospital enrolled, among which 58 patients were newly diagnosed AML-MRC, the patients were followed up and SPSS 25.0 was used to statistically analyze. RESULTS: There were 49 patients performed genetic testing, 29 patients (59.2%) showed chromosomal abnormalities, including 7q- 8 cases (16.3%), 5q- 6 cases (12.2%), 5 cases (10.2%) of 17p abnormalities, 13 cases (26.5%) of highly abnormal complex karyotypes (CK) (≥5 unrelated chromosomal abnormalities), CK contained chromosomal abnormalities such as +8, 5q-, and 12 cases (24.5%) of monosomal karyotypes (MK). Genetic testing was performed in 37 patients, and 24 (64.9%) patients showed genetic mutations, among which ASXL1 mutation was the most common (8 cases, 21.6%), followed by TET2 mutation in 6 cases (16.2%). Kaplan-Meier analysis showed that AML-MRC patients with high CK (P=0.012), 5q- abnormalities (P=0.038), and TP53 mutations (P=0.008) had poor overall survival. CONCLUSION AML-MRC has unique genetic characteristics, and high CK, 5q- and TP53 mutations are poor prognostic factors.
Humans ; Karyotype ; Karyotyping ; Leukemia, Myeloid, Acute/genetics* ; Myelodysplastic Syndromes ; Prognosis

OBJECTIVE: To identify the key genes and explore mechanisms in the development of myelodysplastic syndrome (MDS) by bioinformatics analysis. METHODS: Two cohorts profile datasets of MDS were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed gene (DEG) was screened by GEO2R, functional annotation of DEG was gained from GO database, gene ontology (GO) enrichment analysis was performed via Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and key genes were screened by Matthews correlation coefficient (MCC) based on STRING database. RESULTS: There were 112 DEGs identified, including 85 up-regulated genes and 27 down-regulated genes. GO enrichment analysis showed that biological processes were mainly enriched in immune response, etc, cellular component in cell membrane, etc, and molecular function in protein binding, etc. KEGG signaling pathway analysis showed that main gene enrichment pathways were primary immunodeficiency, hematopoietic cell lineage, B cell receptor signaling pathway, Hippo signaling pathway, and asthma. Three significant modules were screened by Cytoscape software MCODE plug-in, while 10 key node genes (CD19, CD79A, CD79B, EBF1, VPREB1, IRF4, BLNK, RAG1, POU2AF1, IRF8) in protein-protein interaction (PPI) network were screened based on STRING database. CONCLUSION These screened key genes and signaling pathways are helpful to better understand molecular mechanism of MDS, and provide theoretical basis for clinical targeted therapy.
Computational Biology ; Gene Expression ; Gene Expression Profiling ; Humans ; Microarray Analysis ; Myelodysplastic Syndromes/genetics* ; Protein Interaction Maps