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Objective: To investigate the genetic screening methods for cryptic acute promyelocytic leukemia (APL) to further explore its clinical prognosis. Methods: From June 2016 to November 2018, we collected 373 newly diagnosed APL cases. The patients were retrospected by the results of PML-RARα detections both by RT-PCR and i-FISH, those who harbored positive PML-RARα detection by RT-PCR and negative by i-FISH were chosen. Metaphase FISH and Sanger sequencing were further performed to verify these results. Results: A total of 7 cryptic APL cases were discovered. These cases had tiny fragment of RARα inserted into PML in chromosome 15, formed ins (15;17) . The 7 cryptic APL cases had no PML-RARα gene subtype specificity, involving 5 cases in L subtype, 1 case in S subtype and 1 case in V subtype respectively. After the treatment of retinoic acid and arsenic or anthracyclines, 6 cases achieved complete remission, 1 case died of intracranial hemorrhage on the 6th day of therapy. Conclusion: The size and covering position of PML-RARα probe should be taken into account when PML-RARα was performed by FISH on APL patients. Furthermore, combination with Metaphase FISH could improve the recognition of cryptic APL. There were no differences between the cryptic and common APL patients in terms of clinical features and treatment choices. Cryptic APL patients also had a good response to the therapy of retinoic acid and arsenic or anthracyclines.
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Humanos , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 17 , Citogenética , Hibridación Fluorescente in Situ , Leucemia Promielocítica Aguda/genética , Proteínas de Fusión Oncogénica , Receptor alfa de Ácido Retinoico , TretinoinaRESUMEN
Objective: To investigate the clinic-pathological features, diagnosis and treatment of 8p11 myeloproliferative syndrome (EMS) . Methods: Five patients diagnosed as EMS from Jan 2014 to May 2018 at Blood Disease Hospital, Chinese Academy of Medical Sciences were enrolled. The clinical manifestations, laboratory characteristics, treatment and outcome of these patients were summarized. Results: The peripheral blood leukocyte count of 5 patients with EMS increased significantly, accompanied with an elevated absolute eosinophils value (the average as 18.89×10(9)/L) . The hypercellularity of myeloid cells was common in bone marrow, always with the elevated proportion of eosinophils (the average as 17.24%) , but less than 5% of blast cells. The chromosome karyotype of the 5 cases differed from each other, but presenting with the same rearrangement of FGFR1 gene by fluorescence in situ hybridization technology. The average interval between onset and diagnosis was 4.8 months with a median survival of only 14 months. Conclusion: EMS was a rare hematologic malignancy with poor prognosis and short survival. It was commonly to be misdiagnosed. Analysis of cytogenetics and molecular biology were helpful for early diagnosis.
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Humanos , Cromosomas Humanos Par 8 , Eosinofilia/genética , Neoplasias Hematológicas/genética , Hibridación Fluorescente in Situ , Cariotipificación , Enfermedades Linfáticas/genética , Trastornos Mieloproliferativos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Translocación GenéticaRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of loss of heterozygosity(LOH) in HLA region at initial diagnosis and remission of leukemia patient before transplantation on HLA typing.</p><p><b>METHODS</b>The HLA typing was performed in DNA extracted from peripheral blood obtained at diagnosis (Sample 1 and Sample 2) and remission (Sample 3) in one pretransplant male patient with mixedphenotype acute leukemia (MPAL). HLA typing for HLA-A, B, C, DQB1, DRB1 was performed by Sequence-based typing (SBT), Sequence-specific oligonucleotide probe hybridization (SSO) and Sequence-specific primers (SSP). To define more precisely a cutoff limit for the detection of a heterozygous DNA present in a fraction of the cells by the SBT technology, DNA mixing experiments were performed.</p><p><b>RESULTS</b>SBT results showed that Sample 1 and Sample 2 were both homozygous HLA results at five loci (lost one haplotype) although the sequencing background of Sample 1 was a little high. Except HLA-C locus was homozygous, Sample 3 was heterozygous HLA results at four loci. Based on DNA mixing experiments, a cutoff limit for the detection of heterozygous DNA was 20% by SBT technology, and a detection threshold for HLA-A, B, C, DQB1, DRB1 heterozygosity in blood samples was <75% blasts.</p><p><b>CONCLUSION</b>Because LOH may be partial, any homozygous HLA result obtained during a blast crisis, especially ≥75% blasts, would have to be confirmed by a second typing on a buccal swab or on peripheral blood from the patient in complete remission.</p>
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·AIM: To observe the clinical effects of microincision vitrectomy combined with internal limiting membrane (ILM) peeling for high myopia patient with macular hole retinal detachment (MHRD). ·METHODS: This was a retrospective non-randomized controlled clinical study. A total of 26 eyes of 26 patients with high myopic MHRD from January 2011 to December 2016 were included. All eyes underwent 23G pars plana microincision vitrectomy combined with ILM peeling. The preoperative and postoperative best corrected visual acuity ( BCVA ), intraocular pressure, ocular anterior segment and fundus examination were observed, and the anatomical closure of macular hole was checked by optical coherence tomography ( OCT). The relationships between final BCVA and these parameters ( age, GASS stage, onset time, OCT pattern of MH closure, initial vision) were examined by regression analysis. ·RESULTS: The postoperative MH closure rate of high myopia MHRD was 58% . OCT images of the repaired MH in high myopia were categorized into 3 patterns: U-type (3 eyes) with relative normal foveal contour; V-type (4 eyes) with steep foveal contour; W-type (8 eyes) with foveal defect od neruosensory retina, but without warped hem of retinal hole or cystic formation. Multivariate Logistic regression analysis showed that postoperative BCVA was correlated with the OCT patternts of closed MH and initial vision ( P< 0. 05 ). The postoperative visual acuity of U-type closed MH was 6. 9 times higher than that of W-type. ·CONCLUSION: Microincision vitrectomy combined with ILM peeling is a safe and effective surgical treatment for high myopia patient with macular hole retinal detachment. The postoperative visual acuity was correlated with the OCT patterns of closed MH and initial vision.
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Objective: To analyze the clinical and laboratory characteristics, and prognosis of adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. Methods: The medical records of 92 adult AML patients with MLL gene rearrangements from January 2010 to December 2016 were retrospectively analyzed. Results: 92 cases (6.5%) with MLL gene rearrangements were identified in 1 417 adult AML (Non-M(3)) patients, the median age of the patients was 35.5 years (15 to 64 years old) with an equal sex ratio, the median WBC were 21.00(0.42-404.76)×10(9)/L, and 78 patients (84.8%) were acute monoblastic leukemia according to FAB classification. Eleven common partner genes were detected in 32 patients, 9 cases (28.1%) were MLL/AF9(+), 5 cases (15.6%) were MLL/AF6(+), 5 cases (15.6%) were MLL/ELL(+), 2 cases (6.3%) were MLL/AF10(+), 1 case (3.1%) was MLL/SETP6(+), and the remaining 10 patients' partner genes weren't identified. Of 92 patients, 83 cases with a median follow-up of 10.3 (0.3-74.0) months were included for the prognosis analysis, the complete remission (CR) rate was 85.5% (71/83), the median overall survival (OS) and relapse free survival (RFS) were 15.4 and 13.1 months, respectively. Two-year OS and RFS were 36.6% and 29.5%, respectively. Of 31 patients underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT), two-year OS and RFS for patients received and non-received allo-HSCT were 57.9% and 21.4%, 52.7% and 14.9%, respectively (P<0.001). Among patients with partner genes tested, 9 of 32 cases (28.1%) were MLL/AF9(+), the median follow-up was 6.0(4.1-20.7) months. 3 patients with MLL/AF9 underwent allo-HSCT. 23 cases (71.9%) were non- MLL/AF9(+), the median follow-up was 7.8 (0.3-26.6) months. 14 patients (60.1%) with non-MLL/AF9 underwent allo-HSCT. One-year OS for patients with MLL/AF9 and non-MLL/AF9 were 38.1% and 55.5%, respectively (P=0.688). Multivariate analysis revealed that high WBC (RR=1.825, 95% CI 1.022-3.259, P=0.042), one cycle to achieve CR (RR=0.130, 95% CI 0.063-0.267, P<0.001), post-remission treatment with allo-HSCT (RR=0.169, 95% CI 0.079-0.362, P<0.001) were independent prognostic factors affecting OS. Conclusions: AML with MLL gene rearrangements was closely associated with monocytic differentiation, and MLL/AF9 was the most frequent partner gene. Conventional chemotherapy produced a high response rate, but likely to relapse, allo-HSCT may have the potential to further improve the prognosis of this group of patients.
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Adolescente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Adulto Joven , Reordenamiento Génico , Trasplante de Células Madre Hematopoyéticas , N-Metiltransferasa de Histona-Lisina , Leucemia Mieloide Aguda , Proteína de la Leucemia Mieloide-Linfoide , Pronóstico , Estudios RetrospectivosRESUMEN
<p><b>OBJECTIVE</b>To investigate the clinical and cytogenetic characteristics of high-level mixed-lineage leukaemia (MLL) gene amplification in patients with acute myeloid leukemia (AML).</p><p><b>METHODS</b>The clinical and cytogenetic data of 2 AML patients with high-level MLL amplification from January 2010 to August 2016 were analyzed retrospectively.</p><p><b>RESULTS</b>The two AML cases were in middle-aged population. They were diagnosed as FAB subtype M5b and M2a respectively. Both of them had complex karyotypes with the aberrations of chromosome 11. One case was confirmed as MLL-PTD involving exons 2-9 by RT-PCR and sequencing. The other case without MLL-PTD was further analyzed by CytoScan HD analysis. The CMA results showed partial gain of 11q accompanied with partial loss in 11q, deletion of regions in 3p, 3q, 4q, 5q, 7q, 8q, 10p, 10q, 12p and 18q, as well as gain of 4p.</p><p><b>CONCLUSION</b>The co-existence of -5/5q-, -7/7q- and highly complex karyotype may accelerate the poor prognosis. Thus how those cytogenetic abnormalities influencing the disease prognosis need to be further explored.</p>
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To research the effect of Ginseng Radix et Rhizoma and Aconiti Lateralis Radix Praeparata compatibility on cardiac toxicity in rats by UPLC-Q-TOF/MS, and explore the endogenous markers and molecule mechanism. Different compatibility of Shenfu decoction were given to male Wistar rats at dosage of 20 g · kg(-1) for 7 days, collected the serum, and analyze the endogenous metabolites effected by Shenfu formulation by principal component analysis and partial least-squares analysis. Results showed that content of glutathione, phosphatidylcholine and citric acid decreased in mixed-decoction group, while ascorbic acid, uric acid, D-galactose, tryptophan, L-phenylalanine increased. The results showed cardiac toxicity of Aconiti Lateralis Radix Praeparata in Shenfu mixed-decoction. Shenfu co-decoction group showed a similar or weaker trend compared with control group, but most of them do not have a statistically significant. The results indicated the scientific basis of Shenfu compatibility by comparison of co-decoction group with mixed-decoction group. Shenfu compatibility can reduce cardiac toxicity induced by Aconiti Lateralis Radix Praeparata, and citric acid, glutathione, phosphatidyl choline, uric acid might be regarded as potential markers of cardiotoxicity.
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Animales , Masculino , Ratas , Biomarcadores , Cardiotoxicidad , Medicamentos Herbarios Chinos , Toxicidad , Glutatión , Sangre , Análisis de los Mínimos Cuadrados , Metabolómica , Métodos , Análisis de Componente Principal , Ratas WistarRESUMEN
The experiment is designed to explore pathological festures and material basis of pseadoanaphylactoid reaction induced by notoginseng total saponin preparation. Mouse pseadoanaphylactoid reaction was used, 50 ICR mice were randomly assigned to control group, positive medicine group, notoginseng total saponin preparation low-dose group, notoginseng total saponin preparation middle-dose group, notoginseng total saponin preparation high-dose group on average. They are treated by intravenous injection of test substance solutions containing 0.4% Evans blue (EB). 30 min later, scores of ear blue staining and quantitation of ear EB exudation were recorded. Another two experiment were repeated in the same way excluding EB, just to. detect the related cytokines in serum using ELISA. We found that the scores of pseudoanaphylactoid reaction in notoginseng total saponin preparation injection middle-dose group and high-dose group was evidently higher than that in control group, suggesting that notoginseng total saponin preparation injection may be can lead to pseadoanaphylactoid reaction. HE staining showed that pseadoanaphylactoid reaction induced by notoginseng total saponin preparation injection is related to inflammation. Histamine, VEGF and TNF-α levels in notoginseng total saponin preparation middle-dose group and high-dose group significantly increased (P < 0.05, P < 0.01) than control group and showed a dose-dependent manner as well as consistent with the degree of ear blue dye. While IL-6 and IL-10 content did not increase significantly in notoginseng total saponin preparation low-dose group and middle-dose group, but they significantly higher than control group (P < 0.05, P < 0.01) when it increased to quadrupe clinical concentrations, eight times of the clinical dose. So pseadoanaphylactoid reaction caused by notoginseng total saponin preparation may be related to histamine, VEGF, TNF-α, and it is possible that IL-6 and IL-10 can play a role when pseadoanaphylactoid reaction achieve a certain high degree.
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Animales , Ratones , Anafilaxia , Permeabilidad Capilar , Citocinas , Sangre , Relación Dosis-Respuesta a Droga , Hipersensibilidad a las Drogas , Ratones Endogámicos ICR , Panax notoginseng , Química , SaponinasRESUMEN
<p><b>OBJECTIVE</b>To analyze the karyotype stability in hematological malignancies patients before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its prognostic significance of monitoring.</p><p><b>METHODS</b>The karyotypes and clinical data of 21 patients with hematological malignancies at the initial diagnosis and at relapse after allo-HSCT were retrospectively reviewed. Chromosome analysis was performed by standard 24 h-cultured method and R banding.</p><p><b>RESULTS</b>Karyotypes at the initial diagnosis and at relapse after allo-HSCT were different in 11 patients (52.38%), including chromosome 1, 3, 6, 12, 17, 21. Numberical abnormalities and structural chromosomal abnormalities always occurs together. The median survival time of relapse of the patients with karyotype changes was significantly shorter than that of patients without a karyotype change (79 d vs 522 d, P = 0.027), and that of the patients with trisomy 6 was also significantly shorter than that of the patients without trisomy 6 (9 d vs 275 d, P = 0.005).</p><p><b>CONCLUSION</b>Karyotype changes after relapse are associated with the prognosis of allo-HSCT.</p>
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Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Neoplasias Hematológicas , Genética , Cirugía General , Trasplante de Células Madre Hematopoyéticas , Métodos , Cariotipificación , Pronóstico , Estudios RetrospectivosRESUMEN
<p><b>OBJECTIVE</b>To investigate clinical and laboratory characteristics of acute myeloid leukemia (AML) patients with t(7;11)(p15;p15).</p><p><b>METHODS</b>Eleven patients with t(7;11)(p15;p15) were retrospectively reviewed involved in cell morphology, immunophenotype, cytogenetics as well as clinical features and prognosis.</p><p><b>RESULTS</b>Eight patients out of the eleven were female, six patients were AML-M2a, two M4, two M5, and one M6. All the 11 cases expressed CD33, 10 expressed CD117 and CD13, HLA-DR and CD34 was expressed in 7 and 6 patients, respectively. Karyotypes of all the patients were t(7;11) (p115;p15), additional trisomy 8 were found in only one patient. FLT3-ITD was positive in one of nine patients who were analysed for FLT3-ITD and FLT3-TKD. Two patients were alive, and one lost to followed up, while the rest of eight were dead.</p><p><b>CONCLUSION</b>The t(7;11) (p15;p15) abnormalities is one of rare chromosomal translocation in patients with AML. AML patients with t(7;11) (p15;p15) have clinical features of anemia, thrombocytopenia, higher white blood cell, and poor prognosis.</p>