• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3349-3355
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• 2012

Background and objectives: Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome. Methods: We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL1 positive patients had frequent organomegaly and usually presented with a platelets count of less than $50{\times}10^9/l$. Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome. Conclusions: This is the first study from Pakistan which investigated the frequency of5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome. Frequencies of some of the oncogenes were different from those reported elsewhere and they appear to be associated with distinct clinical characteristics and treatment outcome. This information will help in the prognostic stratification and risk adapted management of adult ALL patients.

• Clinical and Experimental Pediatrics
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• v.49 no.2
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• pp.181-186
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• 2006

Purpose : The hematologic change during the treatment of acute lymphoblastic leukemia(ALL) is critical as a prognostic determinant and a variable to determine the dose of chemotherapeutic agents. It is known that the dose of vincristine used in the maintenance phase of ALL is small enough to increase the count of platelet. To investigate the change of platelet count according to the vincristine administration in maintenance phase of ALL chemotherapy, we performed this study. Methods : Eleven patients eligible under the criteria of Children's Cancer Study Group(CCG)-1882 and who had completed chemotherapy were enrolled in this study. The count of platelets before vincristine administration was compared with those of vincristine administration 1, 2 and 3 weeks after the early and last periods of maintenance phases. The platelet count before vincristine administration was defined as 100 percent and that after vincristine were compared. In addition, we tentatively defined an enhancing effect of vincristine as positive when the relative count was more than 120 percent. Results : Platelet count did not differ according to the early and last periods of maintenance phase. Platelet count at first week after vincristine administration increased more significantly than that before vincristine in early and last periods. There was an enhancing effect in 10(90.9 percent) of 11 patients after 1 week vincristine administration both in the early and last periods of the maintenance phase. Conclusion : Vincristine, used in ALL maintenance phases as a low dose, increased platelet count 1 week after administration. The increased platelet count resumed to the previous level 2-3 weeks later. However, the thrombocytosis observed in the maintenance phase by vincristine was not high enough to induce thrombosis. In addition, vincristine is known to reduce the activity of platelets. Therefore, the risk of thrombosis in the maintenance phase of ALL chemotherapy would be low.

• Journal of Yeungnam Medical Science
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• v.10 no.1
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• pp.58-67
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• 1993

The author obtained index of red cell volume distribution width(RDW) and other red cell indices in 210 patients of various hematoncologic conditions and 200 healthy control group using, an automated blood analyzer, Coulter Counter Model S-plus II. This study performed to classify various etiologic anemia based on the MCV and RDW, to evaluate availability to the differential diagnosis in korean anemic distoders somewhat different from etiologies of anemias in foreginers. In the most of cases, the increase or decrease of MCV were always combined the pararell changes of MCH and MCHC. But the values of MCV and RDW were not correlated in control group and patient group. So the terms of heterogenous of homogenous anemia were meaningful morphologic classification than hypochromic or normochromic anemia. The heterogenous microcytic anemia contained iron deficiency anemia. In heterogenous normocytic anemia, myelophthisic anemia, acute leukemia were contained. In heterogenous macrocytic anemia, megaloblastic anemia, hemolytic anemia were contained. The homogenous microcytic anemia was observed in anemia of chronic disorders. In homogenous normocytic anemia, acute blood loss, chronic leukemia, multiple myeloma were contained. The aplastic anemia was belonged to homogenous macrocytic anemia. The diagnostic significance of RDW in hemoglobinopathies is most important. But this study was not contained hemoglobinopathies. Instead RDW was very helpful to differential diagnosis of most common anemias, iron deficiency anemia and anemia due to chronic disorders in Korea.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4353-4358
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• 2014

Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1999-2006
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• 2016

Background: Acute promyelocytic leukemia (APML) is characterized by the reciprocal translocation t(15;17) (p22;p12) resulting in the PML-$RAR{\alpha}$ fusion gene. A dual diagnostic and follow up approach was applied including cytogenetic demonstration of the t(15;17) translocation and detection dg PML-$RAR{\alpha}$ chimeric transcripts by molecular means. Purpose: Conventional cytogenetics involving bone marrow is beset with high probability of poor metaphase index and was substituted with phytohemagglutinin (PHA)-induced peripheral blood culture based cytogenetic analysis as a diagnostic & follow up modality in APML patients of Kashmir (North India). Both qualitative (RT-PCR) and quantitative (Q-PCR) tests were simultaneously carried out to authenticte the modified cytogenetics. Materials and Method: Patient samples were subjected to the said techniques to establish their baseline as well as follow-up status. Results: Initial cytogenetics revealed 30 patients (81%) Positive for t(15;17) whereas 7 (19%) had either cryptic translocation or were negative for t(15;17). Two cases had chromosome 16q deletion and no hallmark translocation t(15;17). Q-PCR status for PML-$RAR{\alpha}$ was found to be positive for all patients. All the APML patients were reassessed at the end of consolidation phase and during maintenance phase of chemotherapy where 6 patients had molecular relapse, wherein 4 also demonstrated cytogenetic relapse. Conclusions: It was found that PHA-induced peripheral blood cytogenetics along with molecular analysis could prove a reliable modality in the diagnosis and assessment of follow up response of APML patients.

• Korean Journal of Psychosomatic Medicine
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• v.11 no.2
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• pp.159-169
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• 2003

Objectives: The object of this study was to compare between perceived stress, coping strategies and quality of life between parents of childhood cancer and normal controls. Methods: Global assessment of recent stress(GARS) scale and symptom checklist-90-revised (SCL-90-R) were used to measure perception for stressors and stress responses(psychopathology). Coping scale and Smithklein Beecham quality of life scale were used to measure coping strategies and quality of life. Results: Scores of perceived stress related to interpersonal, changes in relationship, sickness or illness, financial, unusual happenings on the GARS scale were significantly higher in parents of childhood cancer than normal controls. Scores of the SCL-90-R, somatization, depression, anxiety, hostility subscale were also significantly higher in parents of childhood cancer than normal controls. Scores of self control and positive reappraisal were significantly higher in parents of childhood cancer than normal controls. Parents of childhood cancer scored significantly lower in quality of life than normal controls. Scores of depression were also significantly higher in parents of children diagnosed as acute lymphocytic leukemia(ALL) than those as acute nonlymphocytic leukemia(ANLL). Conclusions: The results suggest that patients with parents of childhood cancer were likely to have higher levels of perceived stressor and psychopathology and lower quality of life than normal controls.

• Journal of Microbiology and Biotechnology
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• v.26 no.2
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• pp.287-294
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• 2016

The effect of kaempferol (3,5,7,4-tetrahydroxyflavone), a flavonoid compound that was identified in barnyard millet (Echinochloa crus-galli var. frumentacea) grains, on G₂-checkpoint and apoptotic pathways was investigated in human acute leukemia Jurkat T cell clones stably transfected with an empty vector (J/Neo) or a Bcl-xL expression vector (J/Bcl-xL). Exposure of J/Neo cells to kaempeferol caused cytotoxicity and activation of the ATM/ATR-Chk1/Chk2 pathway, activating the phosphorylation of p53 (Ser-15), inhibitory phosphorylation of Cdc25C (Ser-216), and inactivation of cyclin-dependent kinase 1 (Cdk1), with resultant G₂-arrest of the cell cycle. Under these conditions, apoptotic events, including upregulation of Bak and PUMA levels, Bak activation, mitochondrial membrane potential (Δψm) loss, activation of caspase-9, -8, and -3, anti-poly (ADP-ribose) polymerase (PARP) cleavage, and accumulation of apoptotic sub-G₁ cells, were induced without accompanying necrosis. However, these apoptotic events, except for upregulation of Bak and PUMA levels, were completely abrogated in J/Bcl-xL cells overexpressing Bcl-xL, suggesting that the G₂-arrest and the Bcl-xL-sensitive mitochondrial apoptotic events were induced, in parallel, as downstream events of the DNA-damage-mediated G₂-checkpoint activation. Together these results demonstrate that kaempferol-mediated antitumor activity toward Jurkat T cells was attributable to G₂-checkpoint activation, which caused not only G₂-arrest of the cell cycle but also activating phosphorylation of p53 (Ser-15) and subsequent induction of mitochondria-dependent apoptotic events, including Bak and PUMA upregulation, Bak activation, Δψm loss, and caspase cascade activation.

• Pediatric Infection and Vaccine
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• v.27 no.3
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• pp.198-204
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• 2020

Cytomegalovirus (CMV) disease is rare in children who receive anticancer chemotherapy and have no history of stem cell transplantation (SCT). We report a case of CMV retinitis that developed during maintenance chemotherapy for acute leukemia. A 7-year-old boy developed decreased visual acuity and persistent pancytopenia during maintenance chemotherapy. Laboratory investigations initially showed significant CMV antigenemia (51 positive cells/200,000 leukocytes); however, antiviral therapy was not deemed necessary in this patient who had no history of SCT. CMV antigenemia worsened to 170 positive cells/200,000 leukocytes over 3 weeks. Ophthalmological examination revealed multiple bilateral retinal infiltrates and granular lesions. He was diagnosed with CMV retinitis and was treated with a 4-week course of intravenous ganciclovir and intravitreal injection of ganciclovir 6 times, followed by a 1-month course of orally administered valganciclovir. A CMV antigenemia assay showed negative results, and follow-up fundoscopy revealed lesser retinal infiltration after the sixth intravitreal ganciclovir injection. Future studies should focus on the development of standardized screening methods and preemptive therapeutic strategies for CMV disease in high-risk children.

• Journal of Ginseng Research
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• v.48 no.3
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• pp.298-309
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• 2024

Background: 20(S)-ginsenoside Rh2(GRh2), an effective natural histone deacetylase inhibitor, can inhibit acute myeloid leukemia (AML) cell proliferation. Lactate regulated histone lactylation, which has different temporal dynamics from acetylation. However, whether the high level of lactylation modification that we first detected in acute promyelocytic leukemia (APL) is associated with all-trans retinoic acid (ATRA) resistance has not been reported. Furthermore, Whether GRh2 can regulate lactylation modification in ATRA-resistant APL remains unknown. Methods: Lactylation and METTL3 expression levels in ATRA-sensitive and ATRA-resistant APL cells were detected by Western blot analysis, qRT-PCR and CO-IP. Flow cytometry (FCM) and APL xenograft mouse models were used to determine the effect of METTL3 and GRh2 on ATRA-resistance. Results: Histone lactylation and METTL3 expression levels were considerably upregulated in ATRA-resistant APL cells. METTL3 was regulated by histone lactylation and direct lactylation modification. Overexpression of METTL3 promoted ATRA-resistance. GRh2 ameliorated ATRA-resistance by downregulated lactylation level and directly inhibiting METTL3. Conclusions: This study suggests that lactylation-modified METTL3 could provide a promising strategy for ameliorating ATRA-resistance in APL, and GRh2 could act as a potential lactylation-modified METTL3 inhibitor to ameliorate ATRA-resistance in APL.

• Tuberculosis and Respiratory Diseases
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• v.49 no.1
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• pp.93-98
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• 2000

Acute respiratory distress syndrome (ARDS) has been reported to be associated with a variety of medical and surgical conditions, including All-trans-retinoic acid (ATTA). ATRA is very efficaceous drug to acute promyelocytic leukemia (APL). This drug can induce complete remission at APL without fatal risk of disseminated intravascular coagulation. But ATRA treatment, sometimes, produces the symptoms of fever, weight gain and acute respiratory distress, renal function impairment. The causes of these symptoms are not fully proved, but supposed as the result of leukostasis and capillary leak syndrome from excessive leukocyte differentiation and cytokines release. Recently, we experienced a 24-year-old woman who complained gum bleeding for 6 days. At bone marrow biopsy, she was diagnosed as APL. 2 days after ATRA treatment, she was suffered from the symptoms of dyspnea and general ache. At laboratory examination, total leukocyte count was 50,400/$mm^3$, $PaO_2$ was 42.5 mm Hg and chest PA revealed the findings compatible with ARDS. Treatment with low dose ara-C, corticosteroid and general supportive cares were tried. Within 3 days after treatment, the patient recovered from ARDS by evidence of arterial blood gas study and chest radiographs. She has acquired complete remission of APL with maintenance of A TRA. And so, we present this case with a review of related literatures.