OBJECTIVE: To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis. METHODS: A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared. RESULTS: The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×10⁹/L, among which 15 cases (68.18%) were >10×10⁹/L, and the median count of platelet (PLT) was 24(4-55)×10⁹/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively. CONCLUSION Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.
Middle Aged ; Humans ; Male ; Female ; Aged ; Leukemia, Myelomonocytic, Acute ; Retrospective Studies ; Leukemia, Myeloid, Acute/diagnosis* ; Prognosis ; Mutation ; Receptors, Colony-Stimulating Factor/genetics*

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*

Objective: To assess the efficacy and toxicity of decitabine-based conditioning regimen in patients with myelodysplastic syndrome (MDS) , acute myeloid leukemia secondary to MDS (MDS-AML) or chronic myelomonocytic leukemia (CMML) . Methods: From March 1, 2013 to May 25, 2015, 22 patients who underwent allogenic hematopoietic stem cell transplantation (allo-HSCT) with decitabine-based conditioning regimen were analyzed retrospectively. Results: ①22 patients, 14 males and 8 females with a median age of 42.5 (24-56) years old, were diagnosed as MDS (n=14) , CMML (n=4) , MDS-AML (n=4) . ②15 patients were treated with the conditioning regimen of decitabine combined with busulfan, cyclophosphamide, fludarabine, and cytarabine, the other 7 cases were treated with decitabine, busulfan, fludarabine, and cytarabine. The dose of decitabine was 20 mg·m(-2)·d(-1) for 5 days.Rabbit anti-human anti-thymocyte globulin (2.5 mg·kg(-1)·d(-1) for 4 days) was involved in conditioning regimen in patients with unrelated donor or haploidentical transplantation. ③Except 1 patient died of infection in 2 months after transplantation, the other patients were engrafted successfully. The median time of granulocyte engraftment was 13 (12-18) days, and the median time of platelet engraftment was 16 (13-81) days. ④The incidence of acute graft versus host disease (aGVHD) was (41.3±10.6) %, and severe aGVHD (grade of III-IV) was (18.4±9.7) %. The incidence of chronic graft versus host disease (cGVHD) was (56.4±11.3) %, and extensive cGVHD was (36.4±12.1) %. ⑤8 patients were suffered with cytomegalovirus (CMV) viremia. Among the 18 patients with definitely infection, 6 occurred during myelosuppression and 12 cases occurred after hematopoietic reconstruction. The 2-year and 3-year non-relapse mortality was (13.9±7.4) % and (24.3±9.5) %, respectively. ⑥The 2-year and 3-year overall survival (OS) was (77.3±8.9) % and (67.9±10.0) %, respectively. The 2-year and 3-year relapse-free survival (RFS) was (72.7±9.5) % and (63.6±10.3) %, respectively. Conclusions: allo-HSCT with decitabine-based conditioning regimen is feasible in the treatment of MDS, MDS-AML or CMML.
Adult ; Busulfan ; Decitabine ; Female ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Leukemia, Myelomonocytic, Chronic ; Male ; Middle Aged ; Myelodysplastic Syndromes ; Retrospective Studies ; Transplantation Conditioning ; Transplantation, Homologous ; Young Adult

No abstract available.
Leukemia, Myelomonocytic, Acute*

BACKGROUND: This retrospective study aimed to characterize and analyze the outcome of therapy-related myeloid neoplasms (t-MNs) in children and adolescents. METHODS: The medical records of 16 patients under 21 years of age at the time of t-MN diagnosis were reviewed. RESULTS: The median patient age was 11.5 years (range, 1.6–20.4 yr). Twelve patients had therapy-related acute myeloid leukemia, 3 patients had myelodysplastic syndrome, and 1 patient had chronic myelomonocytic leukemia. The median latency period was 29 months (range, 11–68 mo). Fourteen patients had cytogenetic aberrations, 8 of whom had an 11q23 abnormality. Of the 13 patients treated with curative intent, 12 patients received myeloid-type induction therapy that led to complete remission (CR) in 8 patients. Nine patients underwent allogeneic transplantation; 4 patients did not undergo transplantation due to chemotherapy-related toxic death (N=3) or parental refusal (N=1). The 5-year overall survival and event-free survival of the 13 patients treated with a curative intent were 46.2% and 30.8%, respectively. For the 9 patients who underwent allogeneic transplantation, the 5-year event-free survival was 66.7%. CONCLUSION: A significant proportion of young patients with t-MNs can experience long-term survival, and allogeneic transplantation plays a key role for attaining cure in these patients.
Adolescent* ; Child* ; Chromosome Aberrations ; Diagnosis ; Disease-Free Survival ; Humans ; Latency Period (Psychology) ; Leukemia, Myeloid, Acute ; Leukemia, Myelomonocytic, Chronic ; Medical Records ; Myelodysplastic Syndromes ; Parents ; Retrospective Studies ; Transplantation, Homologous

No abstract available.
Leukemia, Myeloid, Acute* ; Leukemia, Myelomonocytic, Chronic*

PURPOSE: Systemic disease can manifest oral signs at an early phase, which may be crucial for the diagnosis and timing of treatment. This report describes two patients who presented with gingival enlargement as an early sign of acute leukemia. METHODS: Two patients presented with oral symptoms including severe gingival enlargement. The progress of their symptoms was associated with underlying systemic disease. RESULTS: The patients were transferred to the Department of Hematology and diagnosed with acute myelomonocytic leukemia. They received appropriate treatment and survived. CONCLUSIONS: Gingival enlargement can be caused by underlying systemic diseases. Accurate diagnosis and timely referral are important for preventing a fatal situation. It must be emphasized that some oral signs and symptoms may be closely correlated with systemic diseases.
Dentists ; Diagnosis ; Gingival Hyperplasia ; Hematology ; Humans ; Leukemia* ; Leukemia, Myelomonocytic, Acute ; Referral and Consultation

Additional sex comb-like 1 ( ASXL1) is an enhancer of Trithorax and Polycomb family, which are necessary for the maintenance of stable repression of homeotic and other loci. Recently, alterations of ASXL1 gene were identified in the hematopoietic cells from patients with a variety of myeloid malignancies, including chronic myelomonocytic leukemia (CMML, 43% of cases), myelodysplastic syndrome (MDS, 20%), myeloproliferative neoplasms (MPN, 10%) and acute myeloid leukemia (AML, 20%). The majority of ASXL1 mutations are frameshift and nonsense mutations. These clinical data suggest an important role of ASXL1 in the pathogenesis and/or transformation of myeloid malignancies. However, the role of ASXL1 in the pathogenesis of myeloid malignancies and in normal hematopoiesis in vivo, as well as the underlying mechanisms remains unknown. This article reviews the structure and function of ASXL1, the clinical characteristic and prognostic significance of ASXL1 mutation, the association of ASXL1 with other gene mutation, as well as ASXL1 knock-down or silence in vitro and in vivo models.
Humans ; Leukemia, Myeloid, Acute ; genetics ; Leukemia, Myelomonocytic, Chronic ; genetics ; Mutation ; Myelodysplastic Syndromes ; genetics ; Myeloproliferative Disorders ; genetics ; Repressor Proteins ; genetics

This study was purposed to analyse the immunophenotypic characteristics of chronic myelomonocytic leukemia (CMML), myelodysplastic syndromes (MDS) and acute monocytic leukemia (AML-M5b) by using multiparameter flow cytometry, and to explore its significance in diagnosis and differential diagnosis. The immunophenotypic characteristics of bone marrow samples from 14 CMML patients, 48 MDS patients, 46 AML-M5b patients and 18 normal persons were analyzed and compared by multiparametric flow cytometry. The results showed that the ratio of monocytes in CMML patients was obviously higher than that in MDS, AML-M5b patients and normal persons (P < 0.05), but there was no statistically significant difference between bone marrow samples of MDS and AML-M5b patients as well as normal persons. The ratio of blast cells in MDS patients was obviously higher than that in normal persons (P < 0.05), but did not show significant difference as compared with CMML patients. The ratio of mature granulocytes in AML-M5b patients was obviously lower than that in CMML and MDS patients as well as normal person bone marrow (P < 0.05). Certain differences of CD45/SSC characteristics in MDS, AML-M5b and CMML patients were found in comparison with normal persons. The abnormal expression of CD2, CD56, and CD14 tailing phenomenon were observed in CMML patients in comparison with bone marrow samples of MDS, AML-M5b and normal persons (P < 0.05). Lack and decrease of CD15 expression in MDS and CMML patients was significant different from AML-M5b and normal persons marrow, abnormal expression rate of CD15 in CMML patients was higher than that in MDS patients (P < 0.05), the CD13/CD11b/CD16 abnormal expression of granulocytes was seen in both CMML and MDS patients, but there was no statistically significant difference between them. Other antigens showed abnormality of varying degrees, but did not have any statistical significance. It is concluded that MDS, CMML and AML-M5b displayed a certain degree of similarity, and also possess their own immunophenotype characteristics. Comprehensive analysis of immunophenotype by multiparameter flow cytometry may be important for differential diagnosis among CMML, MDS and AML-M5b. High percentage of monocytes, abnormal coexpression of CD2, CD56 and CD14 tailing phenomenon, lack or decrease of CD15 as well as abnormal expression of CD13/CD11b/CD16 in granulocytes may play important roles in diagnosis of CMML.
Case-Control Studies ; Flow Cytometry ; methods ; Humans ; Immunophenotyping ; methods ; Leukemia, Monocytic, Acute ; diagnosis ; immunology ; Leukemia, Myelomonocytic, Chronic ; diagnosis ; immunology ; Myelodysplastic Syndromes ; diagnosis ; immunology

Abnormalities of chromosome 11 involving mixed lineage leukemia (MLL) on 11q23 are often seen in acute myeloid leukemia (AML)-M5 or AML-M4. The fusion gene of MLL-PTD and MLL plays a critical role in the pathogenesis of these AML. However, rare chromosome abnormalities have been identified in this type of leukemia. To explore whether there were other MLL gene mutations at M4 and M5, in this study all of the MLL exons were sequenced at cDNA level. 25 patients with de novo AML-M4 or M5 with normal karyotypes excluding M4eo and MLL fusion gene or MLL-PTD were selected, the amplification and direct sequencing analysis of full length MLL gene exons were carried out, then the mutations found were verified at genomic DNA level. Furthermore, the point mutations were tested in normal samples and a larger group of AML patients using the platform of Mass Array. The results showed that high-frequency deletion/insertion and point mutations in RD, PHD, TAD and SET domains of MLL were found, while these alterations in normal samples and other subtypes of AML samples were also verified, and without significant difference (P > 0.05). It is concluded that a variety of deletions/insertions in MLL mRNA and point mutations are respectively alternative splicing of MLL gene at transcriptional level and single nucleotide polymorphism. These alternations together constituted genetic polymorphisms of MLL. Although these variations may not play a direct role in the molecular pathogenesis of AML-M4 or M5, their correlations to clinical treatment and prognosis need to be further explored.
Alternative Splicing ; Base Sequence ; Chromosomes, Human, Pair 11 ; genetics ; DNA Mutational Analysis ; Histone-Lysine N-Methyltransferase ; Humans ; Leukemia, Monocytic, Acute ; genetics ; Leukemia, Myelomonocytic, Acute ; genetics ; Molecular Sequence Data ; Mutation ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Oncogene Proteins, Fusion ; genetics