Prenatal diagnosis and genetic analysis of a special case with complex structural rearrangements of chromosome 8 / 中华医学遗传学杂志

OBJECTIVE@#To present on a prenatally diagnosed case with complex structural rearrangements of chromosome 8.@*METHODS@#Chromosome karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) were carried out for a fetus with increased nuchal thickness.@*RESULTS@#The karyotype of the amniotic fluid sample showed extra materials on 8p. FISH revealed a centromeric signal at the terminal of 8p with absence of telomeric signal. CMA revealed partial deletion of 8p23.3 [(208049_2256732)×1], partial duplication of 8p23.3p23.2 [(2259519_3016818)×3], and partial duplication of 8q [8q11.1q12.2(45951900_60989083)×3].@*CONCLUSION@#The complex structural rearrangements of chromosome 8 in this case has differed from the commonly seen inv dup del(8p).

Clinical phenotype and genetic analysis of a fetus with recombinant chromosome 8 syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and molecular genetic mechanism of a fetus with recombinant chromosome 8 (Rec8) syndrome.@*METHODS@#A fetus who was diagnosed with Rec8 syndrome at the Provincial Hospital Affiliated to Shandong First Medical University on July 20, 2021 due to high risk for sex chromosomal aneuploidy indicated by non-invasive prenatal testing (NIPT) (at 21st gestational week) was selected as the study subject. Clinical data of the fetus was collected. G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out on the amniotic fluid sample. Peripheral blood samples of the couple were also subjected to G banded karyotyping analysis.@*RESULTS@#Prenatal ultrasonography at 23rd gestational week revealed hypertelorism, thick lips, renal pelvis separation, intrahepatic echogenic foci, and ventricular septal defect. The karyotype of amniotic fluid was 46,XX,rec(8)(qter→q22.3::p23.1→qter), and CMA was arr[GRCh37]8p23.3p23.1(158049_6793322)×1, 8q22.3q24.3(101712402_146295771)×3. The karyotype of the pregnant woman was 46,XX,inv(8)(p23.1q22.3), whilst that of her husband was normal.@*CONCLUSION@#The Rec8 syndrome in the fetus may be attributed to the pericentric inversion of chromosome 8 in its mother. Molecular testing revealed that the breakpoints of this Rec8 have differed from previously reported ones.

Aspectos citogenéticos y moleculares en los síndromes mielodisplásicos / Cytogenetic and molecular aspects in myelodysplastic syndromes

Introducción: Los síndromes mielodisplásicos constituyen un grupo heterogéneo de alteraciones de la célula progenitora hematopoyética. Estos se caracterizan por presentar una médula ósea hipercelular, una hematopoyesis inefectiva, displasia y citopenia periférica y la posibilidad de evolución a leucemia mieloide aguda. Objetivo: Describir las alteraciones citogenéticas y moleculares más frecuentes de los síndromes mielodisplásicos. Métodos: Se realizó una revisión de la literatura en los idiomas inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico, de artículos publicados en los últimos cinco años. Se realizó análisis y resumen de la bibliografía. Análisis y síntesis de la información: En los síndromes mielodisplásicos están presentes alteraciones citogenéticas frecuentes como la deleción de los cromosomas 5q, 7q y 20q, la monosomía del cromosoma 7, la trisomía del cromosoma 8 y la presencia de cariotipos complejos, que, unido a mutaciones somáticas en diferentes genes, intervienen en la patogénesis de la enfermedad y su conocimiento permite la estratificación pronóstica de los pacientes. Conclusiones: El diagnóstico a través de los estudios citogenéticos convencionales, la hibridación in situ por fluorescencia y la secuenciación génica permite una mayor comprensión de la biología de la enfermedad, la estratificación del riesgo y la toma de decisiones terapéuticas(AU)

Introduction: Myelodysplastic syndromes constitute a heterogeneous group of alterations of the hematopoietic progenitor cell, characterized by hypercellular bone marrow, ineffective hematopoietic, dysplasia and peripheral cytopenia; and the possibility of progressing to acute myeloid leukemia. Objective: To describe the most frequent cytogenetic and molecular alterations of myelodysplastic syndromes. Methods: A review of the literature in English and in Spanish was carried out, in the PubMed website and using the search engine Google, for articles published in the last five years. We performed analysis and summary of the reviewed bibliography. Analysis and synthesis of information: In myelodysplastic syndromes, frequent cytogenetic alterations are present such as deletion of chromosomes 5q, 7q and 20q, as well as the monosomy of chromosome 7, trisomy of chromosome 8 and the presence of complex karyotypes, which together with somatic mutations in different genes intervene in the pathogenesis of the disease and allow prognostic stratification of patients. Conclusions: Diagnosis through conventional cytogenetic studies, fluorescence in situ hybridization and gene sequencing allow a better understanding of the biology of the disease, risk stratification and therapeutic decision making(AU)

Clinical characterization and genetic analysis of a newborn with chromosome 8q21.11 deletion syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology for a newborn with corneal opacity.@*METHODS@#The neonate and her parents were subjected to routine G-banding chromosomal karyotyping analysis. Copy number variation (CNV) was analyzed with low-coverage whole-genome sequencing (WGS) and single nucleotide polymorphism microarray (SNP array).@*RESULTS@#No karyotypic abnormality was found in the newborn and her parents. Low-coverage WGS has identified a de novo 5.5 Mb microdeletion at chromosome 8q21.11-q21.13 in the neonate, which encompassed the ZFHX4 and PEX2 genes. The result was confirmed by SNP array-based CNV analysis.@*CONCLUSION@#The newborn was diagnosed with chromosome 8q21.11 deletion syndrome. ZFHX4 may be one of the key genes underlying this syndrome.

A duplex probe-directed recombinase amplification assay for detection of single nucleotide polymorphisms on 8q24 associated with prostate cancer

Single nucleotide polymorphisms (SNPs) have important application value in the research of population genetics, hereditary diseases, tumors, and drug development. Conventional methods for detecting SNPs are typically based on PCR or DNA sequencing, which is time-consuming, costly, and requires complex instrumentation. In this study, we present a duplex probe-directed recombinase amplification (duplex-PDRA) assay that can perform real-time detection of two SNPs (rs6983267 and rs1447295) in four reactions in two tubes at 39°C within 30 min. The sensitivity of duplex-PDRA was 2×103-104 copies per reaction and no cross-reactivity was observed. A total of 382 clinical samples (179 prostate cancer patients and 203 controls) from northern China were collected and tested by duplex-PDRA assay and direct sequencing. The genotyping results were completely identical. In addition, the association analysis of two SNPs with prostate cancer risk and bone metastasis was conducted. We found that the TT genotype of rs6983267 (OR: 0.42; 95%CI: 0.23-0.78; P=0.005) decreased the risk of prostate cancer, while the CA genotype of rs1447295 (OR: 1.89; 95%CI: 1.20-2.96; P=0.005) increased the risk of prostate cancer. However, no association between the two SNPs (rs6983267 and rs1447295) and bone metastasis in prostate cancer was found in this study (P>0.05). In conclusion, the duplex-PDRA assay is an effective method for the simultaneous detection of two SNPs and shows great potential for widespread use in research and clinical settings.

Characteristic of 8p11 Myeloproliferative Syndrome with Rare Phenotype / 中国实验血液学杂志

OBJECTIVE@#To deeply understand the clinical manifestation, laboratory examination characteristics, diagnosis and treatment of an eight p11 myeloproliferative syndrome (EMS) with rare phenotypes.@*METHODS@#The clinical and laboratory characteristics and the process of allogeneic hematopoietic stem cell transplantation (allo-HSCT) were summarized in 1 rare EMS case involving T/B/myeloid cells. Meanwhile, 2 similar cases in the previous literature were also discussed.@*RESULTS@#The bone marrow examination indicated that the patient with B-cell acute lymphocytic leukemia. The lymph node biopsy showed that the patient was T lymphoblastic/myeloid lymphoma. The 8p11 abnormality was found by the examination of bone marrow chromosomes. The RT-PCR examination showed that the BCR-ABL fused gene was negtive. The FGFR1 breakage was found by using the FISH with FGFR1 probe in lymph node. The Mutation of FMNL3, NBPF1 and RUNX1 genes was found by using the whole exome sequencing. The patient received allo-HSCT under CR2. By the follow-up till to September 2019, the patient survived without the above-mentioned disease.@*CONCLUSION@#EMS manifest as neoplasms involving T-lineage, B-lineage, and myeloid-lineage simultaneously is extremely rare. Although the FGFR1 gene-targeted therapy can be conducted, allo-HSCT should be actively considered.

Prenatal diagnosis of a fetus with 8q13.3 microdeletion through chromosomal microarray analysis / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of chromosomal microarray analysis (CMA) for the prenatal diagnosis of a fetus with structural anomaly detected by ultrasonography.@*METHODS@#The fetus and its parents were subjected to chromosomal karyotyping and CMA analysis.@*RESULTS@#The fetus was found to carry a 46,XN,t(8;11)(q21.2;q13) translocation which was inherited from its mother. CMA has found no copy number variations (CNVs) in both parents but a de novo 2.00 Mb microdeletion in the fetus at 8q13.3.@*CONCLUSION@#CMA is capable of detecting microdeletions and microduplications in fetuses with translocations detected by karyotyping analysis.

Genetic analysis of a family with congenital heart defects caused by chromosome 8p23.1 deletion / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a family affected with congenital heart defects.@*METHODS@#G-banding karyotyping, chromosomal microarray analysis (CMA) and multiplex ligation-dependent probe amplification (MLPA) were carried out to detect copy number variants in a patient with left ventricular noncompaction (LVNC) and his fetus.@*RESULTS@#G-banding karyotyping showed the patient was 45,XY,rob(15;21)(q10;q10)[36]/46,XY[64], while the fetus had an normal karyotype. CMA revealed that both had arr[hg19]8p23.1(11 232 919-11 935 465)×1. MLPA showed both had deletion of all exons of the GATA4 gene.@*CONCLUSION@#The LVNC of the patient and the ventricular septal defect(VSD) of his fetus may result from the same 8p23.1 deletion, for which GATA4 is probably the key gene.

Myeloid/lymphoid neoplasms with eosinophilia and FGFR1 rearrangement: 5 cases report and literatures review / 中华血液学杂志

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.

Clonal evolution and clinical significance of trisomy 8 in acquired bone marrow failure / 中华血液学杂志

Objective: To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure. Methods: The clinical data of 63 patients with acquired bone marrow failure accompanied with isolated trisomy 8 (+8) from June 2011 to September 2018 were analyzed retrospectively, the clonal evolution patterns and relationship with immmunosuppressive therapy were summarized. Results: Totally 24 male and 39 female patients were enrolled, including 39 patients with aplastic anemia (AA) and 24 patients with relatively low-risk myelodysplastic syndrome (MDS) . Mean size of+8 clone in MDS patients[65% (15%-100%) ]was higher than that of AA patients[25% (4.8%-100%) , z=3.48, P=0.001]. The patients were was divided into three groups (<30%, 30%-<50%,and ≥50%) according to the proportion of+8 clone. There was significant difference among the three groups between AA[<30%:55.6% (20/36) ; 30-50%: 22.2% (8/36) ; ≥50%22.2% (8/36) ]and MDS patients[<30%:19.0% (4/21) ; 30%-<50%:19.0% (4/21) ; ≥50%61.9% (13/21) ] (P=0.007) . The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients (P=0.002) ; and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients (P=0.002) . The median age of AA and MDS patients was respectively 28 (7-61) years old and 48.5 (16-72) years old. Moreover, there was no correlation between age and+8 clone size in AA or MDS (r(s)=0.109, P=0.125; r(s)=-0.022, P=0.924, respectively) . There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients (P=0.016, P=0.046, P=0.012, respectively) , but no significant difference in MDS patients. The immunosuppressive therapy (IST) efficacy of AA and MDS patients was respectively 66.7% and 43.8% (P=0.125) . Comparing with initial clone size (27.3%) , the +8 clone size (45%) of AA patients was increased 1-2 year after IST, but no statistical difference (z=0.83, P=0.272) . Consistently, there was no significant change between initial clone size (72.5%) and 1-2 year clone size (70.5%) after IST in MDS patients. There was no significant difference in IST efficient rate between +8 clone size expansion and decline group of in AA patients at 0.5-<1, 1-2 and>2 years after IST. We found four dynamic evolution patterns of +8 clone, which were clone persistence (45%) , clone disappearance (30%) , clone emergence (10%) and clone recurrence (15%) . Conclusions: AA patients had a low clone burden, while MDS patients had a high burden of +8 clone. The +8 clone of AA patients didn't significantly expanded after IST, and the changes of +8 clone also had no effect on IST response.

Phenotypic and genetic analysis of a pedigree with 4p16 microduplication and 8p23 microdeletion / 中华医学遗传学杂志

OBJECTIVE@#To explore the nature and origin of chromosomal copy number variants (CNVs) in a pedigree affected with mental retardation.@*METHODS@#Genomic CNVs of the proband were analyzed by next generation sequencing (NGS). Chromosomal karyotypes of the proband and his relatives were analyzed with high-resolution karyotyping and fluorescence in situ hybridization (FISH).@*RESULTS@#Clinical phenotypes of the proband and other patients from the pedigree included mental retardation and mild dysmorphism. The results of NGS revealed that the proband carried a 16.24 Mb microduplication at 4p16.3-15.32 and a 2.2 Mb microdeletion at 8p23.3-23.2. Other patients of the pedigree harbored the same variants, while those without the phenotypes did not harbor the variants. The results of high-resolution karyotyping and FISH revealed that the mother of the proband carried a reciprocal translocation between 4p and 8p, and her karyotype was 46,XX,t(4;8)(p16;p23). No karyotypic abnormality was detected in his father.@*CONCLUSION@#The abnormal phenotypes of this pedigree may be attributed to 4p microduplication in conjunct with 8p microdeletion derived from a maternal balanced translocation between 4p and 8p.

Clinical Significance of Additional Chromosomal 8 Clonal Evolution in CML Progression / 中国实验血液学杂志

OBJECTIVES@#To explore the clinical significance of clonal evolution of additional chromosomal 8 in CML progression.@*METHODS@#An unusual case with the clonal evolution from trisomy 8 to tetrasomy 8 accompanied by 2 time of CML blast crisis (BC) was reported.@*RESULTS@#This patient suffered from 2 time of CML blast crisis and the additional chromosome 8 aberrations were accompanied. Trisomy 8 and tetrasomy 8 were detected at first CML blast crisis and second CML blast crisis, respectively. After tetrasomy 8 was developed, the c-Myc was over-expressed and the central nervous system leukemia happened in this case. Only high dose Ara-C and MTX regimen could induce remission for a short period.@*CONCLUSION@#These findings suggested that additional chromosome 8 aberrations are important marker for poor prognosis of CML patients and contribute to a poor prognosis.

De Novo San Luis Valley Syndrome-like der(8) Chromosome With a Concomitant dup(8p22) in a Mexican Girl

No abstract available.

Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: description of a new mutation, R384X / Hiperplasia suprarrenal congénita por déficit de 11-beta-hidroxilasa: descripción de una nueva mutación, R384X

Abstract Case Description: It is presented the phenotype of a new compound heterozygous mutation of the genes R384X and Q356X encoding the enzyme of 11-beta-hydroxylase Clinical Findings: Severe virilization, peripheral hypertension, and early puberty. Treatment and Outcome: Managed with hormone replacement therapy (corticosteroid) and antihypertensive therapy (beta-blocker), resulting in the control of physical changes and levels of arterial tension. Clinical Relevance: According to the phenotypic characteristics of the patient, it is inferred that the R384X mutation carries an additional burden on the Q356X mutation, with the latter previously described as a cause of 11-beta-hydroxylase deficiency. The description of a new genotype, as in this case, expands the understanding of the hereditary burden and deciphers the various factors that lead to this pathology as well as the other forms of congenital adrenal hyperplasia (CAH), presenting with a broad spectrum of clinical presentations. This study highlights the importance of a complete description of the patient's CAH genetic profile as well as their parents' genetic profile.

Resumen Descripción del Caso: Se presenta el fenotipo de una nueva mutación heterocigota compuesta en los genes Q356X y R384X que codifican la enzima 11-beta-hidroxilada Hallazgos Clínicos: Virilización severa, pubertad precoz periférica e hipertensión. Tratamiento y Resultados: Manejo con terapia de reemplazo hormonal con corticoide y antihipertensivo con beta-bloqueador con lo que se logró controlar los cambios físicos y los niveles de tensión arterial. Relevancia Clínica: Según las características fenotípicas del paciente se infiere que la mutación R384X acarrea una carga adicional a la mutación Q356X, esta última descrita como causa de deficiencia de 11-beta-hidroxilasa. La descripción de nuevos genotipos, como en este caso, permite ampliar la comprensión de la carga hereditaria y descifrar los diversos factores que llevan a que esta patología, así como las demás formas de hiperplasia suprarrenal congénita (HSC), se presenten con un amplio espectro de cuadros clínicos. Esto permite resaltar la importancia de una descripción completa del perfil genético del paciente con HSC y de sus padres.

Mosaic trisomy 8 detected by fibroblasts cultured of skin / Mosaico trisomía 8 detectada por los cultivos de fibroblastos de la piel

Introduction: Mosaic trisomy 8 or "Warkany's Syndrome" is a chromosomopathy with an estimated prevalance of 1:25,000 to 1:50,000, whose clinical presentation has a wide phenotypic variability. Case Description: Patient aged 14 years old with antecedents of global retardation of development, moderate cognitive deficit and hypothyroidism of possible congenital origin. Clinical Findings: Physical examination revealed palpebral ptosis, small corneas and corectopia, hypoplasia of the upper maxilla and prognathism, dental crowding, high-arched palate, anomalies of the extremities such as digitalization of the thumbs, clinodactyly and bilateral shortening of the fifth finger, shortening of the right femur, columnar deviation and linear brown blotches that followed Blaschko's lines. Cerebral nuclear magnetic resonance revealed type 1 Chiari's malformation and ventriculomegaly. Although the karyotype was normal in peripheral blood (46,XY), based on the finding of cutaneous mosaicism the lesions were biopsied and cytogenetic analysis demonstrated mosaic trisomy 8: mos 47,XY,+8[7]/46,XY[93]. Clinical Relevance: Trisomy 8 is clinically presented as a mosaic, universal cases being unfailingly lethal. In this particular case, cutaneous lesions identified the mosaic in tissue, although the karyotype was normal in peripheral blood. The cutaneous mosaicism represented by brown linear blotches which follow Blaschko's lines is a clinical finding that has not previously been described in Warkany's syndrome.

Introducción: La trisomía 8 en mosaico o Síndrome de Warkany, es una cromosomopatía con una prevalencia estimada de 1:25,000 a 1:50,000, que se presenta clínicamente con una amplia variabilidad fenotípica. Descripción del Caso: Paciente de 14 años con antecedente de retardo global del desarrollo, déficit cognitivo moderado e hipotiroidismo de posible origen congénito. Hallazgos Clínicos: Al examen físico presenta ptosis palpebral, corneas pequeñas y corectopia, hipoplasia de maxilar superior y prognatismo, apiñamiento dental, paladar alto ojival, anomalías en extremidades como digitalización de pulgares, clinodactilia y acortamiento bilateral del quinto dedo en manos, acortamiento de fémur derecho, desviación de columna y máculas lineales pardas que siguen las líneas de Blaschko. En la resonancia nuclear magnética cerebral se aprecia malformación de Chiari tipo 1 y ventriculomegalia. El cariotipo en sangre periférica fue normal (46,XY) sin embargo, ante el hallazgo de mosaicismo cutáneo, se realizó biopsia de las lesiones y su análisis citogenético demostró trisomía 8 en mosaico: mos47,XY,+8[7]/46,XY[93]. Relevancia Clínica: La trisomía 8 se presenta clínicamente en mosaico, los casos universales son indefectiblemente letales. En este caso particular, las lesiones cutáneas identificaron el mosaico en tejido, frente al cariotipo normal en sangre periférica. El mosaicismo cutáneo representado por las máculas lineales pardas (que siguen las líneas de Blaschko) es un hallazgo clínico que no se había descrito en el síndrome de Warkany.

Clinical Prognostic Factors in 86 Chinese Patients with Primary Myelodysplastic Syndromes and Trisomy 8: A Single Institution Experience

PURPOSE: The objective was to determine the characteristics and prognostic factors of 86 Chinese patients with trisomy 8 aberrations and compare the prognostic value of International Prognostic System (IPSS) and Revised IPSS (IPSS-R) in this cohort. MATERIALS AND METHODS: A total of 86 cases diagnosed with primary myelodysplastic syndromes (MDS) with isolated tr8 or with tr8 and other additional cytogenetic aberrations diagnosed and treated at the Union Hospital, Tongji Medical College of Huazhong University of Science and Technology between July 2002 and March 2013 were reviewed. RESULTS: The median survival of the entire group was 23.0 months, and acute myeloid leukemia (AML) developed in 43% (37/86) patients within the follow up time. The univariate analysis revealed that overall survival (OS) was correlated with age, thrombocytopenia, absolute neutrophil count, marrow blasts, cytogenetic status and red blood cell transfusion at diagnosis, and the multivariate analysis revealed that age, marrow blasts, cytogenetic status and transfusion dependence were independent parameters for the OS. The cytogenetic complexity and marrow blasts had the strongest impact on the AML transformation by multivariate analysis. Comparing the two prognostic systems, both two systems could successfully discriminate risk groups for survival. IPSS-R was more refined than IPSS for predicting OS, but had no advantage in predicting the risk of AML development. CONCLUSION: This study confirmed the influence of clinical factors on the prognosis of 86 Chinese MDS patients with trisomy 8. In addition, IPSS-R can further refine prognostic discrimination in the IPSS risk categories.

A t(8;9)(p22;p24)/PCM1-JAK2 Translocation in a Patient With Myeloproliferative Neoplasm and Myeloid Sarcoma: First Report in Korea

No abstract available.

A Novel KIT INDEL Mutation in Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1

No abstract available.

Characteristics and Prognosis of 24 Cases of Primary Acute Myeloid Leukemia with Trisomy 8 / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical features and prognosis of primary acute myeloid leukemia (AML) with trisomy 8.</p><p><b>METHODS</b>The clinical data of 24 cases diagnosed as primary AML with trisomy 8 were collected. The clinical characteristics such as sex, age, subtype of FAB, blood routine and bone marrow blast at the first visit were analyzed and the relationship of the characteristics with CR rate and the prognosis was explored.</p><p><b>RESULTS</b>12 out of 24 AML patients were diagnosed as M5 (50%), while M2, M3, M4 and M6 had 3 cases, respectively (12.5%); one case did not receive the chemotherapy. 23 cases received 1-2 cycles of standard induction chemotherapy. Among them 3 cases of M3 achieved complete response (CR) and survived until the last following up with 100% 5-year OS rate. Among 20 cases of non-M3, 12 cases achieved CR1 (60%), 4 cases achieved partial response (PR) (20%), 4 cases did not respond (NR); 5 cases relapsed in follow-up for 3 years after CR1 (41.7%), 3 cases achieved CR2 after re-induction chemotherapy, and 2 cases remained NR. Among 20 cases of non-M3, 1 case failed to be followed-up after diagnosis within 1 month. The mean follow-up time of 19 cases was 26.2 (1.5-84) months, 9 cases died (6 cases of M5, 1 case of M4 and 2 cases of M2), who achieved PR and NR, or relapsed after CR1; the 3-year DFS and OS were 21%, 31.5% respectively. 2 cases of non-M3 accepted allo-HSCT with HLA-matched sibling donor and kept disease-free survival until the last following up, and survived for 58 and 66 months respectively. Except for 3 cases of M3, 2 cases received allo-HSCT and the cases without chemotherapy, the other 18 cases with initial WBC count less than 10×10(9)/L had OS and DFS longer than those of 10 cases with initial WBC count no less than 10×10(9)/L (P<0.05, P<0.01). The OS of 10 cases with CR1 was longer than OS of those cases without CR1 (P<0.01).</p><p><b>CONCLUSION</b>The incidence of trisomy 8 in M5 is higher than the other AML subtypes, and the prognosis of M5 is poor. The initial WBC count above 10×10(9)/L is a high-risk factor. M3 with trisomy 8 and RARA gene has a very good prognosis. Trisomy 8 may increase the risk of primary AML except for M3, so allo-HSCT with HLA-matched sibling donor should be carried out as much as possible after CR1. The gene mutation of FLT3, MLL, HOX11, C-kit, NPM1 may possess an important significance on prognosis.</p>

Application of fluorescent in situ hybridization in primary diagnosis of aplastic anemia by morphology / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical application of fluorescent in situ hybridization (FISH) for the differential diagnosis of myelodysplastic syndromes (MDS) and aplastic anemia (AA).</p><p><b>METHODS</b>A FISH kit capable of detecting the chromosomal abnormalities related to MDS was used to analyze 94 patients who were suspected to have AA by bone marrow morphology.</p><p><b>RESULTS</b>Cytogenetic abnormalities were detected in 11 of the 94 patients, which included trisomy 8 (5 cases), 20q- (1 case) and -Y (1 case). There were 4 cases related to MDS, which included 3 cases of 5q-, in which 1 case carry 20q- at the same time, and 7q- (1 case). No significant difference was found between the MDS and AA groups in terms of age, sex or routine blood examination including absolute neutrophil count, hemoglobin content and platelet count.</p><p><b>CONCLUSION</b>FISH can detect certain cytogenetic abnormalities related to MDS in patients morphologically diagnosed as AA.</p>