1.Monitoring of WT-1 gene expression in peripheral blood of patients with acute leukemia by semiquantitative RT-PCR; possible marker for detection of minimal residual leukemia.
Seong Cheol KIM ; Nae Choon YOO ; Jee Sook HAHN ; Seok LEE ; So Young CHONG ; Yoo Hong MIN ; Yun Woong KO
Yonsei Medical Journal 1997;38(4):212-219
The expression of the WT-1 gene which is found exclusively in human leukemic blasts frequently disappears from bone marrow of leukemia patients in complete remission (CR). Using semiquantitative RT-PCR, we investigated the expression of the WT-1 gene in peripheral bloods (PBs) of 33 patients with acute leukemia (AML 26; ALL 7) and monitored its expression after achievement of CR. None of the 6 normal controls expressed detectable levels of WT-1 transcripts (< 10(-4), background level), whereas 31 (93.9%) of 33 patients expressed variable levels of WT-1 transcripts (range, 10(-4) to 10(1)) at diagnosis. The level of WT-1 expression was not different between AML and ALL. By monitoring WT-1 gene expression in PB of 31 patients during CR, 5 patients relapsed (two from the 18 patients with undetectable levels of WT-1 gene expression and three from the 13 with WT-1 gene expression in low levels). Three of the 5 relapsed patients showed preceding reappearance or rise of WT-1 gene expression. From these results, we reconfirmed that the WT-1 gene is a pan-acute leukemic marker, which can be used to monitor minimal residual leukemia (MRL) after chemotherapy or in patients with CR.
Gene Expression/physiology*
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Human
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Leukemia, Lymphocytic, Acute/genetics*
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Leukemia, Lymphocytic, Acute/blood*
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Leukemia, Myelocytic, Acute/genetics*
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Leukemia, Myelocytic, Acute/blood*
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Neoplasm, Residual
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Nephroblastoma/genetics*
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Polymerase Chain Reaction
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Transcription, Genetic
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Tumor Markers, Biological
2.Myelodysplastic syndrome that progressed to acute myelomonocytic leukemia with eosinophilia showing peculiar chromosomal abnormality: a case report.
Seong Ho KIM ; Cheol Won SUH ; Seong Jun CHOI ; Jung Gyun KIM ; Je Hwan LEE ; Sung Bae KIM ; Sang We KIM ; Kyoo Hyung LEE ; Jung Shin LEE ; Woo Kun KIM ; Sang Hee KIM ; Eul Ju SEO ; Hyun Sook CHI
Journal of Korean Medical Science 1999;14(4):448-450
Myelodysplastic syndrome is a closely related group of acquired bone marrow disorders characterized by ineffective and dysplastic hematopoiesis. These clonal disorders frequently progress to acute leukemia. Acute myelomonocytic leukemia with eosinophilia is characterized by an increase in abnormal eosinophils in the bone marrow, relatively good clinical course and inv (16) chromosomal abnormality. We experienced one case of refractory anemia with excess blasts which progressed to refractory anemia with excess blasts in transformation and finally to acute myelomonocytic leukemia with eosinophilia showing peculiar chromosomal abnormalities of der (1;7).
Adult
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Anemia/pathology
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Anemia/genetics
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Anemia/etiology
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Bone Marrow/pathology
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Case Report
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Chromosomes, Human, Pair 16*
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Disease Progression
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Eosinophilia/pathology
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Eosinophilia/genetics*
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Eosinophilia/etiology
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Human
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Inversion (Genetics)*
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Karyotyping
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Leukemia, Myelocytic, Acute/pathology
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Leukemia, Myelocytic, Acute/genetics*
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Leukemia, Myelocytic, Acute/etiology
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Male
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Myelodysplastic Syndromes/pathology
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Myelodysplastic Syndromes/genetics*
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Myelodysplastic Syndromes/complications
3.Prognostic Significance of Multidrug Resistance Gene 1 (MDR1), Multidrug Resistance-related Protein (MRP) and Lung Resistance Protein (LRP) mRNA Expression in Acute Leukemia.
Hee Jin HUH ; Chan Jeoung PARK ; Seongsoo JANG ; Eul Ju SEO ; Hyun Sook CHI ; Je Hwan LEE ; Kyoo Hyung LEE ; Jong Jin SEO ; Hyung Nam MOON ; Thad GHIM
Journal of Korean Medical Science 2006;21(2):253-258
The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to beta-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1 %, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.
Vault Ribonucleoprotein Particles/*genetics
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Survival Rate
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RNA, Neoplasm/genetics
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RNA, Messenger/genetics
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Prognosis
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Neoplasm Proteins/*genetics
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Multidrug Resistance-Associated Proteins/*genetics
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Middle Aged
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Male
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Leukemia, Myelocytic, Acute/drug therapy/genetics/mortality
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Leukemia, Lymphocytic, Acute/drug therapy/genetics/mortality
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Leukemia/drug therapy/*genetics/mortality
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Infant
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Humans
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*Genes, MDR
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Gene Expression
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Female
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Child, Preschool
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Child
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Base Sequence
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Aged
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Adult
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Adolescent
4.The experimental and clinical study on the effect of curcumin on cell cycle proteins and regulating proteins of apoptosis in acute myelogenous leukemia.
Yan, CHEN ; Yudan, WU ; Jing, HE ; Wenjuan, CHEN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2002;22(4):295-8
To investigate whether the Bcl-2 gene family is involved in modulating mechanism of apoptosis and change of cell cycle protein induced by curcumin in acute myeloid leukemia HL-60 cell line and primary acute myelogenous leukemic cells, the Bcl-2 family member Mcl-1, Bax and Bak and cell cycle proteins including P27kipl, P21wafl, cyclin D3 and pRbp- were selected and their expression detected by SABC immuno-histochemical stain method. The attitude of sub-G1 peak in DNA histogram was determined by FCM. The TUNEL positive cell percentage was identified by terminal deoxynucleotidyl transferase (TdT)-mediated Biotin dUNP end labeling technique. It was found that when HL-60 cells were treated with 25 mumol/L curcumin for 24 h, the expression level of Mcl-1 was down-regulated, but that of Bax and Bak up-regulated time-dependently. There was significant difference in the expression level of Mcl-1, Bax and Bak between the curcumin-treated groups and control group (P < 0.05-0.01). At the same time, curcumin had no effect on progress of cell cycle in primaty acute myelogenous leukemia at newly diagnosis, but could increase the peak of Sub-G1 (P < 0.05), and down-regulate the expression of Mcl-1 and up-regulate the expression of Bax and Bak with the difference being statistically significant. The expression of P27kipl, P21wafl and pRbp- were elevated and that of cyclin D3 decreased in the presence of curcumin. These findings suggested that the Bcl-2 gene family indeed participated in the regulatory process of apoptosis induced by curcumin in HL-60 cells and AML cells. Curcumin can induce apoptosis of primary acute myelogenous leukemic cells and disturb cell cycle progression of HL-60 cells. The mechanism appeared to be mediated by perturbing G0/G1 phases checkpoints which associated with up-regulation of P27kipl, P21wafl and pRbp- expression, and down-regulation of cyclin D3.
Antineoplastic Agents, Phytogenic/pharmacology
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Apoptosis/*drug effects
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Cell Cycle Proteins/*metabolism
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Curcumin/*pharmacology
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Genes, bcl-2/genetics
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HL-60 Cells
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Leukemia, Myelocytic, Acute/pathology
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Neoplasm Proteins/biosynthesis
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Neoplasm Proteins/genetics
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Proto-Oncogene Proteins/biosynthesis
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Proto-Oncogene Proteins/genetics
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Proto-Oncogene Proteins c-bcl-2/*metabolism
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Tumor Cells, Cultured
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bcl-2-Associated X Protein