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      급성림프구성백혈병에서 면역조직화학염색에 의한 p16 단백질 소실의 의의 = Clinical significance of loss of p16 protein by immunohistochemicalstaining in acute lymphoblastic leukemia

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      https://www.riss.kr/link?id=A104551300

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      다국어 초록 (Multilingual Abstract)

      Purpose:p16 gene, mapped to the 9p21 chromosomal region, has emerged as a candidate tumor suppressor gene in human neoplasm. It is an inhibitor of cyclin-dependent kinase and inhibits Rb phosphorylation. In a variety of tumors including childhood acut...

      Purpose:p16 gene, mapped to the 9p21 chromosomal region, has emerged as a candidate tumor suppressor gene in human neoplasm. It is an inhibitor of cyclin-dependent kinase and inhibits Rb phosphorylation. In a variety of tumors including childhood acute lymphoblastic leukemia (ALL), deletion and/or mutation of the p16 gene has been found. Despite their high frequency, the prognostic importance of p16 alterations is still controversial in ALL and has been reported to be either unfavorable or similar to that of other patients. We studied the correlation between loss of p16 protein confirmed by immunohistochemical staining and clinical outcomes of patients diagnosed as ALL.
      Methods:We performed an immunohistochemical staining for p16 protein in 74 cases of bone marrow biopsy slide initially diagnosed as ALL between January 1998 and December 2006. We reviewed the clinical manifestations, laboratory findings, treatment outcomes retrospectively.
      Results:Of 74 slides, 12 were negative for p16 protein. Seven were males and 5 were females with a median age at diagnosis was 5.8 (1.3-18.8) years. Initial WBC were 17,225 (500-403,300)/µL. By immunologic surface marker analysis, 7 patients were early pre-B CALLA (+) and 5 patients were T-cell ALL. Two patients of intermediate risk group had relapsed and died. Three patients had family history of breast cancer. Four patients died and overall survival rates were 53.5±18.7%.
      Conclusion:Loss of p16 protein is supposed to be an independent risk factor of childhood ALL associated with poor outcomes. In clinical setting, the clinician must take into account p16 status, not only at the genomic but also at the protein level. Further clinical experience on thoroughly investigated cases will help a better understanding between p16 status and clinical outcomes. (Korean J Pediatr 2008;51:73-77)

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      다국어 초록 (Multilingual Abstract)

      Purpose:p16 gene, mapped to the 9p21 chromosomal region, has emerged as a candidate tumor suppressor gene in human neoplasm. It is an inhibitor of cyclin-dependent kinase and inhibits Rb phosphorylation. In a variety of tumors including childhood acut...

      Purpose:p16 gene, mapped to the 9p21 chromosomal region, has emerged as a candidate tumor suppressor gene in human neoplasm. It is an inhibitor of cyclin-dependent kinase and inhibits Rb phosphorylation. In a variety of tumors including childhood acute lymphoblastic leukemia (ALL), deletion and/or mutation of the p16 gene has been found. Despite their high frequency, the prognostic importance of p16 alterations is still controversial in ALL and has been reported to be either unfavorable or similar to that of other patients. We studied the correlation between loss of p16 protein confirmed by immunohistochemical staining and clinical outcomes of patients diagnosed as ALL.
      Methods:We performed an immunohistochemical staining for p16 protein in 74 cases of bone marrow biopsy slide initially diagnosed as ALL between January 1998 and December 2006. We reviewed the clinical manifestations, laboratory findings, treatment outcomes retrospectively.
      Results:Of 74 slides, 12 were negative for p16 protein. Seven were males and 5 were females with a median age at diagnosis was 5.8 (1.3-18.8) years. Initial WBC were 17,225 (500-403,300)/µL. By immunologic surface marker analysis, 7 patients were early pre-B CALLA (+) and 5 patients were T-cell ALL. Two patients of intermediate risk group had relapsed and died. Three patients had family history of breast cancer. Four patients died and overall survival rates were 53.5±18.7%.
      Conclusion:Loss of p16 protein is supposed to be an independent risk factor of childhood ALL associated with poor outcomes. In clinical setting, the clinician must take into account p16 status, not only at the genomic but also at the protein level. Further clinical experience on thoroughly investigated cases will help a better understanding between p16 status and clinical outcomes. (Korean J Pediatr 2008;51:73-77)

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      참고문헌 (Reference)

      1 Gonzalgo ML, "The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines" 58 : 1245-1252, 1998

      2 Mirebeau D, "The prognostic significance of CDKN2A, CDKN2B and MTAP inactivation in B-lineage acute lymphoblastic leukemia of childhood. Results of the EORTC studies 58881 and 58951" 91 : 881-885, 2006

      3 Kim DH, "TEL-AML1 translocations with TEL and CDKN2 inactivation in acute lymphoblastic leukemia cell lines" 88 : 785-794, 1996

      4 Nomdedeu JF, "TEL rearrangements in acute lymphobalstic leukemia: association with p16 deletions in relapsed cases" 86 : 547-548, 2001

      5 Schultz KR, "Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG)" 109 : 926-935, 2007

      6 Cooley LD, "Prognostic significance of cytogenetically detected chromosome 21 anomalies in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study" 175 : 117-124, 2007

      7 Heyman M, "Prognostic importance of p15INK4B and p16INK4 gene inactivation in childhood acute lymphocytic leukemia" 14 : 1512-1520, 1996

      8 Tutor O, "Loss of heterozygosity of p16 correlates with minimal residual disease at the end of the induction therapy in non-high risk childhood B-cell precursor acute lymphoblastic leukemia" 26 : 817-820, 2002

      9 Takasaki Y, "Interruption of p16 gene expression in adult T-cell leukaemia/lymphoma: clinical correlation" 122 : 253-259, 2003

      10 Conter V, "Intensive BFM chemotherapy for childhood ALL: interim analysis of the AIEOP-ALL 91 study. Associazione Italiana Ematologia Oncologia Pediatrica" 83 : 791-799, 1998

      1 Gonzalgo ML, "The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines" 58 : 1245-1252, 1998

      2 Mirebeau D, "The prognostic significance of CDKN2A, CDKN2B and MTAP inactivation in B-lineage acute lymphoblastic leukemia of childhood. Results of the EORTC studies 58881 and 58951" 91 : 881-885, 2006

      3 Kim DH, "TEL-AML1 translocations with TEL and CDKN2 inactivation in acute lymphoblastic leukemia cell lines" 88 : 785-794, 1996

      4 Nomdedeu JF, "TEL rearrangements in acute lymphobalstic leukemia: association with p16 deletions in relapsed cases" 86 : 547-548, 2001

      5 Schultz KR, "Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG)" 109 : 926-935, 2007

      6 Cooley LD, "Prognostic significance of cytogenetically detected chromosome 21 anomalies in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study" 175 : 117-124, 2007

      7 Heyman M, "Prognostic importance of p15INK4B and p16INK4 gene inactivation in childhood acute lymphocytic leukemia" 14 : 1512-1520, 1996

      8 Tutor O, "Loss of heterozygosity of p16 correlates with minimal residual disease at the end of the induction therapy in non-high risk childhood B-cell precursor acute lymphoblastic leukemia" 26 : 817-820, 2002

      9 Takasaki Y, "Interruption of p16 gene expression in adult T-cell leukaemia/lymphoma: clinical correlation" 122 : 253-259, 2003

      10 Conter V, "Intensive BFM chemotherapy for childhood ALL: interim analysis of the AIEOP-ALL 91 study. Associazione Italiana Ematologia Oncologia Pediatrica" 83 : 791-799, 1998

      11 Geradts J, "Immunohistochemical detection of the cyclin-dependent kinase inhibitor 2/multiple tumor suppressor gene 1 (CDKN2/MTS1) product p16INK4A in archival human solid tumors: correlation with retinoblastoma protein expression" 55 : 6006-6011, 1995

      12 Sharpless NE, "INK4a/ARF: a multifunctional tumor suppressor locus" 576 : 22-38, 2005

      13 Kees UR, "Homozygous deletion of the p16/MTS1 gene in pediatric acute lymphoblastic leukemia is associated with unfavorable clinical outcome" 89 : 4161-4166, 1997

      14 Rubnitz JE, "Genetic studies of childhood acute lymphoblastic leukemia with emphasis on p16, MLL, and ETV6 gene abnormalities: results of St Jude Total Therapy Study XII" 11 : 1201-1206, 1997

      15 Okuda T, "Frequent deletion of p16INK4a/MTS1 and p15INK4b/MTS2 in pediatric acute lymphoblastic leukemia" 85 : 2321-2330, 1995

      16 Choi J, "Expression of Livin, an antiapoptotic protein, is an independent favorable prognostic factor in childhood acute lymphoblastic leukemia" 109 : 471-477, 2007

      17 Kim NR, "Epstein-Barr virus and p16INK4A methylation in squamous cell carcinoma and precancerous lesions of the cervix uteri" 20 : 636-642, 2005

      18 Bertin R, "CDKN2A, CDKN2B and MTAP gene dosage permits precise characterization of mono- and bi-allelic 9p21 deletions in childhood acute lymphoblastic leukemia" 37 : 44-57, 2003

      19 Van Zutven LJ, "CDKN2 deletions have no prognostic value in childhood precursor-B acute lymphoblastic leukaemia" 19 : 1281-1284, 2005

      20 Lee DS, "Application of high throughput cell array technology to FISH: investigation of the role of deletion of p16 gene in leukemias" 127 : 355-360, 2007

      21 Kamb A, "A cell cycle regulator potentially involved in genesis of many tumor types" 264 : 436-440, 1994

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      연월일 이력구분 이력상세 등재구분
      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
      2020-01-15 학술지명변경 한글명 : Korean Journal of Pediatrics -> Clinical and Experimental Pediatrics
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      2020-01-01 평가 등재학술지 유지 (해외등재 학술지 평가) KCI등재
      2019-07-16 학회명변경 한글명 : 대한소아과학회 -> 대한소아청소년과학회 KCI등재
      2010-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-01-30 학술지명변경 한글명 : 소아과 -> Korean Journal of Pediatrics KCI등재
      2008-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2006-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2003-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2002-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.18 0.18 0.16
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.17 0.2 0.369 0.06
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