Three Novel Variants of t(8;21) and Classical t(8;21) Translocation in Acute Myeloid Leukemia.

BACKGROUND: Some studies have discussed adverse prognosis factors of AML with t(8;21) to be closely related to genetic changes. METHOD: We reviewed 58 cases of AML in children and adults with t(8;21)(q22;q22) translocation. RESULTS: Five variant translocation cases were observed: t(8;17;21)(q22;q12;q22) (case 1), t(1;8;21)(q12;q22;q22) (case 2), and t(8;12;21)(q22;p13;q22) (case 3). The translocations were first observed in three children. Case 2 was cured with chemotherapy, and the cut-off date of observation was 120 months. Case 3 relapsed after 1 year (overall survival [OS], 14 months). Patients with AML with t(8;21) variant translocation have different prognoses and require further study. Forty-two of the 58 cases were included in the survival analysis. Cox regression analysis showed that progression-free survival (PFS) was correlated with age group, white blood cell (WBC) count, bone marrow blast ratio, and loss of Y chromosome (-Y). Overall survival (OS) was correlated with age group, WBC count, and -Y. Childhood leukemia with t(8;21) has a better prognosis than adult leukemia. Survival curves were drawn according to age and cytogenetic abnormalities. CONCLUSIONS: Progression-free survival was correlated with age, white blood cell (WBC) count, bone marrow blast ratio, and loss of Y chromosome (-Y). OS was correlated with age group, WBC count, and -Y chromosome. Child-hood leukemia with t(8;21) has a better prognosis than adult leukemia.

Retrospective Study of Three Cases of Congenital Leukemia with Clinical Presentations and Particular Cytogenetic Abnormality.

BACKGROUND: The goal is to assess the prognosis of cytogenetic abnormality, because cytogenetic abnormality is rarely encountered in clinical practice. METHODS: We retrospectively report three cytogenetic abnormality cases with clinical, cytogenetic, and genetic characteristic. RESULTS: All cases occurred within one month of birth and had prominent hepatosplenomegaly, including acute myeloid leukemia (case 1, case 2) and acute leukemia (case 3). Moreover, case 1 appeared as leukemia cutis at birth, case 2 was born with respiratory distress, and both showed hyperleukocytosis. The R-banded karyotype detected cytogenetic abnormality in three cases, case 1 with 46,XY,t(8;12)(q21;p13), case 2 with 47,XX,+21 and case 3 with 46,XY,t(6;X)(q22:p12), respectively. Especially in case 1, reverse transcription-polymerase chain reaction analysis showed MLL-AF10 rearranged. CONCLUSIONS: In our studies, all cases had not received chemotherapy and survived about 1 - 2 months. It suggests that cytogenetic disorders are closely related to disease development and likely result in fatal outcome if untreated. Thus, we proposed that a proper treatment decision is urgently needed in congenital leukemia.

Isochromosome 11q is Associated with Unique Characteristics and Poor Prognosis in Patients with Acute Myeloid Leukemia.

BACKGROUND: Isochromosome 11q in patients with acute myeloid leukemia is rarely reported, and little is known about its main features. METHODS: The presence of isochromosome 11q was identified in four patients (three adults and one child) from screening 441 patients with an acute myeloid leukemia diagnosis between 2009 and 2018 by using R-banding and fluorescence in situ hybridization. RESULTS: The child, patient 1 with unreported isochromosome (partial 11q isochromosome), accompanied with t(1;11) translocation, initially achieved remission after receiving chemotherapy. However, 4 months later this patient experienced a relapse. While multiple treatments were tried, it had no effect and the patient survived for 16 months. The remaining patients with isochromosome 11q exhibited numerical/structural chromosomal abnormal-ities involving myelodysplastic syndrome-related chromosomes 5, 7, 8, and 20. In patients 2 and 3, we found a derivative chromosome 21. Patient 3 was newly diagnosed with acute myeloid leukemia and was treated with many chemotherapy protocols, unfortunately with no effect. The patient then received traditional Chinese medicine and survived for 10 months, although she still has not achieved complete remission. Patients 2 and 4 received chemotherapy but experienced rapid disease progression and died within 2 months. CONCLUSIONS: In summary, patients with isochromosome 11q/partial 11q isochromosome have a poorer prognosis, especially for isochromosome 11q. Furthermore, these chromosome aberrations may be risk factors for the presence of isochromosome 11q or myelodysplastic syndrome-related genes, both of them may be associated with a failure to respond to treatment and poor outcomes. Hence, these discoveries may lay a foundation to study mechanisms and explore treatments.

Assisted Reproductive Technology Outcomes in Women with Normal Ovarian Response Receiving Recombinant Luteinizing Hormone/Human Menopausal Gonadotropin: An Observational Study.

Objective: Additive human menopausal gonadotropin (HMG)/recombinant luteinizing hormone (r-LH) to follicle-stimulating hormone (FSH) can improve pregnancy outcomes in patients with poor ovarian response during assisted reproductive procedures. However, their effects on patients with normal ovarian response during such procedures are unclear, which formed the aim of this study. Methods: This retrospective study enrolled 456 infertile women who underwent in vitro fertilization or intracytoplasmic sperm injection treatment. Group 1 received FSH; Group 2 received FSH+HMG/r-LH; Group 3 received FSH+HMG+r-LH. Results: The age and Body Mass Index were significantly greater in Group III. The endometrial thickness was greater in Groups II and III, suggesting better endometrial receptivity. Better pregnancy and birth outcomes were seen in Group 3. In sub-cohorts of women older than 32 years old or with overweight/obesity, pregnancy and birth outcomes were also much better in Group 3, albeit without statistical significance. Conclusion: The addition of both HMG and r-LH to FSH may improve the chance of infertile women with normal ovarian responses to have more success in having live birth babies, specifically in those over 32 years of age or with overweight/obese patients who typically face challenges in conceiving and sustaining a pregnancy.

Involvement of MMP-9 in collagen degradation of sea bass (Lateolabrax japonicus): Cloning, expression, and characterization.

Disintegration of intramuscular connective tissue is responsible for postmortem tenderization of fish muscles during chilled storage. Matrix metalloproteinase-9 (MMP-9) was reported to be involved in this process, whereas the mechanism has not been revealed. In the present study, purified type I and V collagens from the connective tissues of sea bass (Lateolabrax japonicus) muscles were first prepared. These two kinds of collagens comprise three polypeptide chains (α), forming a typical triple-helical domain as determined by circular dichroism. The complete coding region of MMP-9 containing an open reading frame of 2070 bp encoding 689 amino acid residues was then cloned. The recombinant MMP-9 catalytic domain (rcMMP-9) was expressed in Escherichia coli and exhibited high hydrolyzing activity toward gelatin. Besides, rcMMP-9 was effective in degrading type V collagen rather than type I collagen at 4°C. The enzymatic activity of rcMMP-9 was highly pH-dependent, and its enzymatic activity under neutral and basic conditions was higher than that under acidic conditions. Metal ion Ca2+ was necessary for the maintenance of rcMMP-9 activity, whereas Zn2+ inhibited its activity. Our present study indicated that MMP-9 is responsible for the disintegration of intramuscular connective tissues by cleaving type V collagen during postmortem tenderization of fish muscle. PRACTICAL APPLICATION: Elucidation the involvement of MMP-9 in collagen degradation will deliver a reference for the prevention of muscular protein decomposition during chilled storage of fish fillets.

Identification of chromosomal abnormalities and genomic features in near-triploidy/tetraploidy-acute leukemia by fluorescence in situ hybridization.

BACKGROUND: Near-triploidy/tetraploidy is rarely found in acute leukemia. Only limited data are available to characterize this condition, and it remains largely unknown. PATIENTS AND METHODS: In our study, we performed karyotype analysis on 1,031 patients diagnosed with acute leukemia from 2006 to 2018. A total of 10 patients of near-triploidy/tetraploidy karyotype were enrolled. Two cases of near-triploidy (66-79 chromosomes) and eight cases of near-tetraploidy (84-100 chromosomes) were identified. Bone marrow samples of these 10 patients were analyzed by fluorescence in situ hybridization with 19 commercially available probes that detected a small portion of gene alterations and large regions of chromosome amplifications. RESULTS: Of the six patients with acute myelocytic leukemia, we detected three cases of double t(8;21)(q22;q22) that have not been previously reported, and one of them demonstrated ins(21;8) (q22;q24q22). We also describe a novel pediatric case carrying double t(15;17)(q22;q21) and receiving targeted treatment with all-trans retinoic acid therapy. To date, this case has responded well to the regimen and has shown continuous complete remission. All patients received chemotherapy. One of them received allogeneic hematopoietic stem cell transplant (HSCT) and survived for 22 months. Eight of the 10 patients died, and the median overall survival was 11 months. CONCLUSION: Using fluorescence in situ hybridization, we identified the distinct complex karyotype of near-triploidy/tetraploidy and provided further prognostic information. Tetraploidy acute promyelocytic leukemia had favorable prognosis; thus, HSCT was not necessary. The case of insertion t(21;8)(q22;q24q22) in tetraploidy responded poorly to chemotherapy and achieved molecular remission with difficultly. Data from patients in this group indicated that near-triploidy/tetraploidy acute leukemia has poor prognosis and new therapy is urgently needed.

Purification, Characterization, and Crystal Structure of Parvalbumins, the Major Allergens in Mustelus griseus.

Fish play important roles in human nutrition and health, but also trigger allergic reactions in some population. Parvalbumin (PV) represents the major allergen of fish. While IgE cross-reactivity to PV in various bony fish species has been well characterized, little information is available about allergens in cartilaginous fish. In this study, two shark PV isoforms (named as SPV-I and SPV-II) from Mustelus griseus were purified. Their identities were further confirmed by mass spectroscopic analysis. IgE immunoblot analysis showed that sera from fish-allergic patients reacted to both SPV-I and SPV-II, but the majority of sera reacted more intensely to SPV-I than SPV-II. Thermal denaturation monitored by CD spectrum showed that both of the SPV allergens are highly thermostable. SPV-I maintained its IgE-binding capability after heat denaturation, while the IgE-binding capability of SPV-II was reduced. The results of crystal structure showed that SPV-I and SPV-II were similar in their overall tertiary structure, but their amino acid sequences shared lower similarities, indicating that the differences in the IgE-binding capabilities of SPV-I and SPV-II might be due to differential antigen epitopes in these two isoforms.

Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation.

X-linked juvenile retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding retinoschisin (RS1), which leads to a significant proportion of visual impairment and blindness. To develop personalized genome editing based gene therapy, knock-in animal disease models that have the exact mutation identified in the patients is extremely crucial, and that the way which genome editing in knock-in animals could be easily transferred to the patients. Here we recruited a family diagnosed with XLRS and identified the causative mutation (RS1, p.Y65X), then a knock-in mouse model harboring this disease-causative mutation was generated via TALEN (transcription activator-like effector nucleases). We found that the b-wave amplitude of the ERG of the RS1-KI mice was significantly decreased. Moreover, we observed that the structure of retina in RS1-KI mice has become disordered, including the disarray of inner nuclear layer and outer nuclear layer, chaos of outer plexiform layer, decreased inner segments of photoreceptor and the loss of outer segments. The novel knock-in mice (RS1-KI) harboring patient-specific mutation will be valuable for development of treatment via genome editing mediated gene correction.