High-Throughput Sequencing Technology for Detection of Gene Mutations in Myeloid Malignancies and Its Clinical Prognostic Significance / 中国实验血液学杂志

OBJECTIVE@#To detect the gene mutations in patients with myeloid malignancies by high-throughput sequencing and explore the correlation between gene mutations and prognosis.@*METHODS@#A retrospective analysis was performed on 56 patients with myeloid malignancies who were hospitalized in the department of hematology, Peking University International Hospital from January 2020 to May 2021. The genetic mutations of the patients were detected by next-generation sequencing technology, and the correlation between the genetic mutations and prognosis of myeloid malignancies was analyzed.@*RESULTS@#In 56 patients, the number of mutated genes detected in a single patient is 0-9, with a median of 3. Sequencing results showed that the most common mutated genes were RUNX1(21.4%), TET2(17.9%), DNMT3A(17.9%), TP53(14.3%) and ASXL1(14.3%), among which the most common mutations occurred in the signaling pathway-related genes (23.3%) and the transcription factor genes (18.3%). 84% of the patients carried multiple mutated genes (≥2), and correlation analysis showed there were obvious co-occurring mutations between WT1 and FLT3, NPM1 and FLT3-ITD, and MYC and FLT3. TP53 mutation was more common in MDS patients.The overall survival time of patients with NRAS mutation was significantly shortened (P =0.049). The prognosis of patients with TP53 mutation was poor compared with those without TP53 mutation, but the difference wasn't statistically significant (P =0.08).@*CONCLUSION@#The application of next-generation sequencing technology is of great significance in myeloid malignancies, which is helpful to better understand the pathogenesis of the disease, to judge the prognosis and to find possible therapeutic targets.

Two Cases of Trisomy 19 as a Sole Chromosomal Abnormality in Myeloid Disorders / 대한진단검사의학회지

Trisomy 19 is frequently encountered in cases of chronic myeloid leukemia (CML) as a secondary abnormality: however, trisomy 19 rarely occurs as a sole chromosomal abnormality and, to date, it has only been reported in 48 hematopoietic malignancies, 1 case of adenocarcinoma and 1 case of astrocytic tumor. Here, we report two additional cases of trisomy 19 as a sole karyotypic aberration in myeloid malignancies. One of these cases involved a 6-month-old male who was diagnosed with acute myeloid leukemia minimally differentiated. His karyotype was 47,XY,+19[20]. He expired 5 days after diagnosis. Another case occurred in an 80-yr-old female who had refractory anemia with excess blasts. Her karyotype was 47,XX,+19[16]/46,XX[4]. Four months later, her peripheral blood smears suggested that the disease had progressed, but she refused further evaluation. Based on a review of the existing literature and the results of this report, trisomy 19 not only as a secondary abnormality but also as a sole karyotypic aberration is strongly associated with myeloid disorder; however, it is not preferentially found in specific FAB subgroups of myelodysplasic syndrome or acute myeloid leukemia.

Cytogenetical, Morphological, and Immunophenotypical Characteristics of Myeloid Malignancies with t (8;21) / 대한혈액학회지

BACKGROUND: Myeloid malignancies carrying t (8;21) (q22;q22) exhibit several characteristic features. This translocation is most often associated with acute myeloid leukemia with maturation (AML-M2), but rarely with myelodysplastic syndrome. We studied the correlation of cytogenetics, morphology, and immunophenotype in 21 myeloid malignancies carrying t (8;21). METHODS: We analyzed 21 t (8;21) positive myeloid malignancies for morphology, immunophenotype and cytogenetics, retrospectively. We also performed reverse transcription polymerase chain reaction (RT-PCR) for AML1-ETO fusion transcripts using marrow slides stored at room temperature. RESULTS: 17 patients were diagnosed as French-American-British (FAB) type M2 and 4 cases as refractory anemia with excess blasts in transformation (RAEB-t). Three patients had marrow eosinophilia and 14 cases (67%) had Auer rods in leukemic blasts. Three patients (14%) developed granulocytic sarcomas. Four patients had variant t (8;21) translocation and 16 (76%) had secondary clonal abnormalities, most commonly loss of a sex chromosome (52%). 15 patients (83%) aberrantly expressed CD19. AML1-ETO fusion transcript of same size was observed in classic and variant t (8;21) translocation (11/14, 79%). CONCLUSION: Our study showed that myeloid malignancies carrying t (8;21) have distinctive morphological, immunophenotypical, and molecular features. These results can be aid to understand the pathogenesis and stratify treatment of those malignancies in the future.