RESUMO
<p><b>OBJECTIVE</b>To observe the biological characteristic and the prognoses in patients with acute erythroleukemia (AEL).</p><p><b>METHODS</b>The results of 167 patients with newly diagnosed AEL, from January 2003 and June 2013 in the First Affiliated Hospital of Soochow University, were reviewed by MICM.</p><p><b>RESULTS</b>Flow cytometry analysis indicated that CD13(96.1%), CD33(95.1%), CD117(87.4%) and CD34 (79.4%) were highly expressed in AEL. 56 of 148 (37.8%) AEL patients had a variety of cytogenetic abnormalities, 27 of 148(18.2%) patients were complex karyotype (abnormalities involving 3 or more chromosomes), the abnormalities of chromosomes 3, 5, 7 and 8 were more frequently involved and the most common one was +8, accounting for 35.7% of all abnormal karyotype, followed by 5q- (17.9%). Mutation analysis showed CEBPA mutation ratio of AEL patients was 44.0% (11/25), that of NPM1 as 15.4% (4/26). Initial induced remission rate of AEL was 56.6% (30/53), compared by 33.3% (4/12) of MDSM6. Survival analysis showed that the overall survival in female was better than that in male (P=0.047). The overall survival time of transplantation group is significantly longer than chemotherapy group (P=0.000). The OS of 13-39 years old group was the best, 40-49 years old group took second place, >50 years old group appeared to be the worst.</p><p><b>CONCLUSION</b>AEL had its own unique biological features, and allogeneic hematopoietic stem cell transplantation could significantly improve its poor prognosis.</p>
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Leucemia Eritroblástica Aguda , Diagnóstico , Prognóstico , Indução de RemissãoRESUMO
The present study was designed to investigate the prevalence and clinical significance of SIL-TAL1 rearrangements in T-cell acute lymphoblastic leukemia (T-ALL). The incidence of SIL-TAL1 rearrangements was analyzed by nest real-time quantitative polymerase chain reaction (RT-PCR) in 68 patients with T-ALL. Karyotypic analysis was performed by conventional R-banding assay and array-based comparative genomic hybridization (array-CGH). The results showed that SIL-TAL1 rearrangements were identified in 10/26 (38.5%) pediatric and 2/42 (4.8%) adult T-ALL cases, which indicate a pediatric preference for SIL-TAL1 rearrangements in T-ALL. Two different transcripts were detected in 6/12(50%) T-ALL samples. Abnormal karyotypes were detected in 6 out of 11 cases (54.5%) and a deletion of the long arm of chromosome 6 was observed in 4 cases. Array-CGH results of 2 T-ALL cases with SIL-TAL1 rearrangement revealed that this fusion gene was resulted from a cryptic deletion of 1p32, and the overlap region of 6q deletion was 6q14.1-16.3. These cases with SIL-TAL1 fusion had a higher white blood cell (WBC) count and higher serum levels of lactate dehydrogenase (LDH) than cases without SIL-TAL1 fusion. It is concluded that SIL-TAL1 rearrangements are associated with loss of heterozygosity of chromosomal 6q, and SIL-TAL1-positive patients are younger than SIL-TAL1-negative patients. In contrast to the cases without SIL-TAL1 fusion, there are many adverse prognostic factors in the cases with SIL-TAL1 fusion, such as higher WBC count and higher LDH levels.
Assuntos
Humanos , Deleção Cromossômica , Cromossomos Humanos Par 6 , Hibridização Genômica Comparativa , Leucemia-Linfoma de Células T do Adulto , Proteínas de Fusão Oncogênica , Genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The purpose of this study was to summary the clinical and laboratorial features in 15 adult cases of mixed phenotypic acute leukemia with Ph chromosome and/or BCR-ABL fusion gene positive (Ph(+)MPAL), 15 adult patients with Ph(+)MPAL were defined by WHO-2008 classification. The clinical characteristics, results of morphology, immunology, cytogenetics and molecular genetic detections and results of follow-up in 15 adult patients with Ph(+)MPAL were analyzed retrospectively. The results showed that 15 patients among 87 cases of MPAL demonstrated Ph(+)MPAL (17.2%; 15/87) (7 males and 8 females), their median age was 51 (range 16-81) year old and median WBC count at diagnosis was 69 (12.7-921)×10(9)/L. Based on FAB criteria, these patients showed different morphologic types, including AML (13.3%; 2/15), ALL (40.0%; 6/15), HAL (46.7%; 7/15). Immunologic analysis indicated that 15 cases of Ph(-)MPAL were all classified as B-lymphoid +myeloid mixed immunophenotype. Except one patient, all expressed CD34 antigen on the surface of leukemia cells with 64.3% strong positive, only Ph (53.3%; 8/15), Ph with additional chromosomal abnormalities (33.3%; 5/15) and normal karyotype (13.3%; 2/15) were cytogenetically identified. BCR-ABL fusion gene transcript positive were detected by multiplex reverse transcription PCR in all cases, with e1a2 subtype (p190) (40.0%; 6/15) and b2a2 or b3a2 (p210) subtype (60.0%; 9/15). Four out of 7 (57.1%) patients were found to have IKZF1 gene deletion, without other common gene mutations. Seven out of 10 cases (70.0%) achieved complete remission (CR) after one cycle of induction chemotherapy. In the induction stage, CR rate seemed higher when tyrosine kinase inhibitors (TKI) were added to chemotherapy (83.3%:50.0%; P = 0.206). Overall survival (OS) in 4 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was longer than that in 4 patients received chemotherapy alone (P = 0.004). It is concluded that Ph(+)MPAL mainly is expressed as B+My phenotype. The majority of patients is older and has CD34 overexpression. In the aspect of molecular genetics, the Ph(+)MPAL is similar to other acute leukemia with Ph chromosome. Ph(+)MPAL is a subtype of acute leukemia with poor prognosis. WBC count at diagnosis is an independent prognostic factor. The combination of TKI and allo-HSCT can improve their long-term survival, which needs to be confirmed through carrying out a prospective and multicenter clinical trial for newly diagnosed Ph(+)MPAL.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antígenos CD34 , Metabolismo , Proteínas de Fusão bcr-abl , Genética , Metabolismo , Transplante de Células-Tronco Hematopoéticas , Cariotipagem , Fenótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras , Diagnóstico , Genética , Terapêutica , Prognóstico , Inibidores de Proteínas Quinases , Usos Terapêuticos , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
This study was aimed to investigate the occurrence and clinical significance of the SET-NUP214 fusion gene in patients with T-cell acute lymphoblastic leukemia (T-ALL), analyse clinical and biological characteristics in this disease. RT-PCR was used to detect the expression of SET-NUP214 fusion gene in 58 T-ALL cases. Interphase FISH and Array-CGH were used to detect the deletion of 9q34. Direct sequencing was applied to detect mutations of PHF6 and NOTCH1. The results showed that 6 out of 58 T-ALL cases (10.3%) were detected to have the SET-NUP214 fusion gene by RT-PCR. Besides T-lineage antigens, expression of CD13 and(or) CD33 were detected in all the 6 cases. Deletions of 9q34 were detected in 4 out of the 6 patients by FISH. Array-CGH results of 3 SET-NUP214 positive T-ALL patients confirmed that this fusion gene was resulted from a cryptic deletion of 9q34.11q34.13. PHF6 and NOTCH1 gene mutations were found in 4 and 5 out of 6 SET-NUP214 positive T-ALL patients, respectively. It is concluded that SET-NUP214 fusion gene is often resulted from del(9)(q34). PHF6 and NOTCH1 mutations may be potential leukemogenic event in SET-NUP214 fusion gene.