• Clinical and Experimental Pediatrics
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• v.54 no.3
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• pp.106-110
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• 2011

In pediatric patients with acute lymphoblastic leukemia (ALL), the Philadelphia chromosome translocation is uncommon, with a frequency of less than 5%. However, it is classified as a high or very high risk, and only 20-30% of Philadelphia chromosome-positive (Ph+) children with ALL are cured with chemotherapy alone. Allogeneic hematopoietic stem cell transplantation from a closely matched donor cures 60% of patients in first complete remission. Recent data suggest that chemotherapy plus tyrosine kinase inhibitors (TKIs) may be the initial treatment of choice for Ph+ ALL in children. However, longer observation is required to determine whether long-term outcome with intensive imatinib and chemotherapy is indeed equivalent to that with allogeneic related or alternative donor hematopoietic stem cell transplantation (HSCT). Reports on the use of second-generation TKIs in children with Ph+ ALL are limited. A few case reports have indicated the feasibility and clinical benefit of using dasatinib as salvage therapy enabling HSCT. However, more extensive data from clinical trials are needed to determine whether the administration of second-generation TKIs in children is comparable to that in adults. Because Ph+ ALL is rare in children, the question of whether HSCT could be a dispensable part of their therapy may not be answered for some time. An international multicenter study is needed to answer the question of whether imatinib plus chemotherapy could replace sibling allogeneic HSCT in children with Ph+ ALL.

• BMB Reports
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• v.29 no.3
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• pp.241-247
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• 1996

The Philadelphia (Ph) chromosome is the single most intensively studied chromosome alteration characterizing a human malignancy. The specific genetic alteration of chronic myelogenous leukemia (CML) is the formation of the BCR/abl fusion gene in leukemic cells. The presence of the BCR/abl gene has important diagnostic and prognostic implications in CML. The detection of BCR/abl transcripts by reverse transcriptase based polymerase chain reaction (RT-PCR) was investigated in patients with CML in whom the Ph chromosome abnormality was documented by cytogenetic analysis. In a total of 68 CML patient cases, the Ph chromosome was found in 53 cases (77.9%) by cytogenetic analysis. On the other hand, sixty two cases (91.2%) were detected to have BCR/abl gene rearrangement Of these, b3a2 was 44 cases (64.7%) and b2a2 was 17 cases (25,0%). There was one case with both b3a2 and b2a2 (1.5%). Of the fifteen cases of Ph chromosome negative by cytogenetic anlaysis, the BCR/abl gene was observed in nine cases, The results of BCR/abl fusion gene confirmed by the direct sequencing method correlated well with PCR analysis, The amplified PCR products were detected by $1{\times}10^{-5}$ dilutions. In conclusion, PCR technique is sensitive, rapid and relatively simple for a laboratory test in detecting the BCR/abl fusion gene with CML regardless of the result of cytogenetic analysis.

• Journal of Microbiology and Biotechnology
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• v.16 no.7
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• pp.1068-1077
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• 2006

Pseudomonas sp. PhCN strain, which has the potential to utilize phenol and cyanide as a sole carbon and nitrogen source, was isolated. A comparison of the effect of cyanide on phenol degradation and vice versa by strain PhCN showed that the degradation time was significantly delayed by an increase in either phenol or cyanide concentration, and the greatest activities were obtained in basal medium containing a low concentration of cyanide and phenol. This strain contained two plasmids of approximately 120 kb (pPhCN-1) and 110 kb (pPhCN-2). Plasmid curing experiments produced a plasmid-free strain as well as strains containing either the 120- or the 110 kb plasmid. The strains were tested for their ability to utilize phenol and KCN. The results demonstrated that the ability to utilize phenol was encoded by the 120 kb plasmid, whereas the ability to utilize cyanide appeared to be encoded by the chromosome.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3793-3797
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• 2015

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of pluripotent stem cells, caused by reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11), known as the Philadelphia chromosome. Materials and Methods: A total of 51 CML patients were recruited in this study. Complete blood counts of all CML patients were performed to find out their total leukocytes, hemoglobin and platelets. FISH was performed for the detection of BCR-ABL fusion and cryptogenic tests using bone marrow samples were performed for the conformation of Ph (9;22)(q34;q11) and variant translocation mechanisms. Results: In cytogenetic analysis we observed that out of 51 CML patients 40 (88.9%) were Ph positive and 4 (8.88%) had Ph negative chromosomes. Mean values of WBC 134.5 $10^3/{\mu}l$, hemoglobin 10.44 mg/dl, and platelets 288.6 $10^3/{\mu}l$ were observed in this study. Conclusions: In this study, Ph positive translocation between chromosome (9:22)(q34;q11) were observed in 40 (88.9%) CML patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5013-5018
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• 2015

Background: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid lineages. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical Philadelphia chromosome (Ph)-negative MPN that have a Janus Kinase 2 (JAK2) mutation, especially JAK2V617F in the majority of patients. The major complications of Ph-negative MPNs are thrombosis, hemorrhage, and leukemic transformation. Objective: To study clinical manifestations including symptoms, signs, laboratory findings, and JAK2V617F mutations of Ph-negative MPN (PV, ET and PMF) as well as their complications. Materials and Methods: All Ph-negative MPN (PV, ET and PMF) patients who attended the Hematology Clinic at Maharaj Nakorn Chiang Mai Hospital from January, 1 2003 through December, 31 2013 were retrospectively reviewed for demographic data, clinical characteristics, complete blood count, JAK2V617F mutation analysis, treatment, and complications. Results: One hundred and fifty seven patients were included in the study. They were classified as PV, ET and PMF for 68, 83 and 6 with median ages of 60, 61, and 68 years, respectively. JAK2V617F mutations were detected in 88%, 69%, and 100% of PV, ET and PMF patients. PV had the highest incidence of thrombosis (PV 29%, ET 14%, and PMF 0%) that occurred in both arterial and venous sites whereas PMF had the highest incidence of bleeding (PMF 17%, ET 11%, and PV 7%). During follow up, there was one ET patient that transformed to acute leukemia and five cases that developed thrombosis (three ET and two PV patients). No secondary myelofibrosis and death cases were encountered. Conclusions: Ph-negative MPNs have various clinical manifestations. JAK2V617F mutations are present in the majority of PV, ET, and PMF patients. This study confirmed that thrombosis and bleeding are the most significant complications in patients with Ph-negative MPN.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.481-488
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• 2022

Background: Although the tumor-suppressive effects of ginsenosides in cell cycle have been well established, their pharmacological properties in mitosis have not been clarified yet. The chromosomal instability resulting from dysregulated mitotic processes is usually increased in cancer. In this study, we aimed to investigate the anticancer effects of ginsenoside Rg1 on mitotic progression in cancer. Materials and methods: Cancer cells were treated with ginsenoside Rg1 and their morphology and intensity of different protein were analyzed using immunofluorescence microscopy. The level of proteins in chromosomes was compared through chromosomal fractionation and Western blot analyses. The location and intensity of proteins in the chromosome were confirmed through immunostaining of mitotic chromosome after spreading. The colony formation assays were conducted using various cancer cell lines. Results: Ginsenoside Rg1 reduced cancer cell proliferation in some cancers through inducing mitotic arrest. Mechanistically, it inhibits the phosphorylation of histone H3 Thr3 (H3T3ph) mediated by Haspin kinase and concomitant recruitment of chromosomal passenger complex (CPC) to the centromere. Depletion of Aurora B at the centromere led to abnormal centromere integrity and spindle dynamics, thereby causing mitotic defects, such as increase in the width of the metaphase plate and spindle instability, resulting in delayed mitotic progression and cancer cell proliferation. Conclusion: Ginsenoside Rg1 reduces the level of Aurora B at the centromere via perturbing Haspin kinase activity and concurrent H3T3ph. Therefore, ginsenoside Rg1 suppresses cancer cell proliferation through impeding mitotic processes, such as chromosome alignment and spindle dynamics, upon depletion of Aurora B from the centromere.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.66 no.4
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• pp.318-325
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• 2021

The objective of this study was to identify the effect of zebularine, a DNA methylation inhibitor, on the chromosomal association between homoeologous chromosomes in the wheat genetic background. Zebularine at a final concentration of 10 µM was used to treat the spikes of the double monosomic wheat addition line (DMA) with one Leymus mollis chromosome and one Leymus racemosus chromosome, both of which were in a homoeologous relationship. In late prophase, zebularine led to chromosome breakage in the Leymus homoeologous chromosomes. Chromosome breakage caused an increase in the frequency of chromosomal associations between the Leymus homoeologous chromosomes. Ordinary DMA showed 65 cells (35.3%) with chromosomal associations and 119 cells (64.7%) with no association, whereas treated DMA showed 102 cells (60.0%) with chromosomal associations and 67 cells (39.4%) with no association. In diakinesis, the Leymus bivalent showed a chromosomal association in the whole euchromatic region. In metaphase, the Leymus bivalent showed association in the whole chromosomal region, unlike other Leymus bivalents with partial chromosomal association. Chromosomal association by chromosome breakage occurred not only between Leymus chromosomes but also between Leymus and wheat chromosomes. The frequency of other chromosomal association (such as fusion and insert) was increased. Chromosome breakage by zebularine treatment is a useful method at the chromosome level as the spores with others are hereditary stable, although the homologous index (h) was not significantly different between ordinary DMA and treated DMA. It is necessary to study how to control zebularine treatment with a more stable concentration for chromosome breakage during meiosis.

• Clinical and Experimental Pediatrics
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• v.60 no.5
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• pp.129-137
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• 2017

The event-free survival (EFS) for pediatric acute lymphoblastic leukemia (ALL) has shown remarkable improvement in the past several decades. In Korea also, a recent study showed 10-year EFS of 78.5%. Much of the improved outcome for pediatric ALL stems from the accurate identification of prognostic factors, the designation of risk group based on these factors, and treatment of appropriate duration and intensity according to risk group, done within the setting of cooperative clinical trials. The schema of first-line therapy for ALL remains mostly unchanged, although many groups have now reported on the elimination of cranial irradiation in all patients with low rates of central nervous system relapse. Specific high risk subgroups, such as Philadelphia chromosome-positive (Ph+) ALL and infant ALL continue to have significantly lower survival than other ALL patients. The introduction of tyrosine kinase inhibitors into therapy has led to enhanced outcome for Ph+ ALL patients. Infant ALL patients, particularly those with MLL rearrangements, continue to have poor outcome, despite treatment intensification including allogeneic hematopoietic cell transplantation. Relapsed ALL is a leading cause of mortality in pediatric cancer. Recent advances in immunotherapy targeting the CD19 of the ALL blast have shown remarkable efficacy in some of these relapsed and refractory patients. With improved survival, much of the current focus is on decreasing the long-term toxicities of treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2159-2164
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• 2016

Background: A diagnosis of chronic myeloid leukemia (CML) is made on discovery of the presence of a Philadelphia (Ph) chromosome. The success of the treatment of this form of leukemia with tyrosine kinase inhibitor (TKI) is monitored by reduction of the Ph chromosome. Objective: To compare the role of conventional cytogenetic (CC) methods with a real time quantitative polymerase chain reaction (RQ-PCR) and fluorescence in situ hybridization (FISH) for diagnosis and treatment monitoring of CML patients. The secondary outcome was to analyze the treatment responses to TKI in CML patients. Materials and Methods: This was a retrospective study of CML patients who attended the Hematology clinic at Chiang Mai University Hospital from 2005-2010. Medical records were reviewed for demographic data, risk score, treatment response and the results of CC methods, FISH and RQ-PCR. Results: One hundred and twenty three cases were included in the study, 57.7% of whom were male with a mean age of 46.9 years. Most of the patients registered as intermediate to high risk on the Sokal score. At diagnosis, 121 patients were tested using the CC method and 118 (95.9%) were identified as positive. Five patients failed to be diagnosed by CC methods but were positive for BCR-ABL1 using the FISH method. Imatinib was the first-line treatment used in 120 patients (97.6%). In most patients (108 out of 122, 88.5%), a complete cytogenetic response (CCyR) was achieved after TKI therapy and in 86 patients (70.5%) CCyR was achieved long term by the CC method. Five out of the 35 analyzed patients in which CCyR was achieved by the CC method had a positive FISH result. Out of the 76 patients in which CCyR was achieved, RQ-PCR classified patients to only CCyR in 17 patients (22.4%) with a deeper major molecular response (MMR) in 4 patients (5.3%) and complete molecular response (CMR) in 55 patients (72.4%). In the case of initial therapy, CCyR was achieved in 95 patients (79.1%) who received imatinib and in both patients who received dasatinib (100%). For the second line treatment, nilotinib were used in 30 patients and in 19 of them (63.3%) CCyR was achieved. In half of the 6 patients (50%) who received dasatinib as second line or third line treatment CCyR was also achieved. Conclusions: CML patients had a good response to TKI treatment. FISH could be useful for diagnosis in cases where CC analysis failed to detect the Ph chromosome. RQ-PCR was helpful in detecting any residual disease and determining the depth of the treatment response at levels greater than the CC methods.

• Journal of Aquaculture
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• v.11 no.1
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• pp.77-81
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• 1998

Cytogenetic analyses were carried out with induced hybrid between common carp (Cyprinus carpio) female and crucian carp (Carassius auratus) male. The erythrocytic measurement revealed that cellular and nuclear size of induced hybrids were intermediate between those of paremtal species. The modal chromosome numbers of common carp, crucian carp and its hybid were same as 2n=100. The DNA content of induced hybrids determined based on flow cytometry was 3.7pg/cell which corresponding to intermediate value between the carp (3.6ph/cell) and crucian carp (3.8pg/cell)