혈액종양의 분자세포유전학 Molecular Cytogenetics in hematologic Malignancy

백혈병과 관련된 세포유전학 역사 1960 Ph chromosome 1970 Banding technique 1977 t(15;17), t(4;11) 1979 High-resolution banding technique 1980 1982 t(9;11) in AML-M5a, inv(3) in AML 1983 del(16q), inv(16) in AML-M4E 1984 t(1;3) in AML with dysmegakaryopoiesis t(1;19) in ALL ISCN (1985,1991,1995)

Cytogenetic & Gene Rearrangement 1980 1983 MYC-IGH t(8;14) 1984 ABL-BCR t(9;22), IGH-BCL2 t(14;18) 1988 ATRA in APL Tx 1990 1991 MLL t(4;11), PBX1-E2A t(1;19) PML-RARA t(15;17), AML1-ETO t(8;21) DEK-CAN t(6;9) 1993 CBFB-MYH11 inv(16), MLL-AF9 t(9;11)

Leukemia in Cinema 비밀 가을동화 안녕 내사랑 태양은 가득히 Last Concert Love Story Dying Young Marvin’s Room Roman Holiday

Dedicato A Una Stella 1976, Italy Richard Johnson Pamela Villoresi 불치 병(백혈병)에 걸린 아가씨와 오랜 슬럼프에 빠진 피아니스트의 슬픈 사랑을 엮은 러브스토리

having to say you're sorry Love means never having to say you're sorry Starring Ali MacGraw, Ryan O'Neal, John Marley Erich Segal, 1970

AML-M2 with t(8;21)(q22;q22) Usually AML-M2, occasionally M1 & M4 Young individuals with good remission rate Blasts containing a single thin Auer rod RT-PCR : AML1/ETO fusion transcript

AML-M3 with t(15;17) The most specific clinical association in AML RT-PCR : PML/RARA fusion transcript Responsive to retinoic acid treatment

AML-M4Eo with Inv(16) Young patients, organomegaly, abnormal eosinophils Specifically associated with M4Eo in over 50% of cases Favorable prognosis, High incidence of CNS relapse MYH11 CBFB CBFB-MYH11

It’s not just a love story. 사랑을 위하여 (1991) It’s not just a love story. It’s a life story Starring Julia Roberts Campbell Scott Music by Kenneth Gorelick 자유분방한 사고를 가진 노동자계층의 여자가 백혈병으로 시한부 인생을 사는 상류계층의 청년을 간호하기 위해 고용된다. 그리고 둘은 사랑에 빠진다.

장호태 (박상민) 강민기 (유준상) 박지숙 (김지수) KBS 2TV 주말연속극 2000.10.-2001. 3.18 장호태 (박상민) 강민기 (유준상) 박지숙 (김지수) 강한 태양(인간의 욕망)은 강한 그림자를 남긴다

가을동화 KBS 미니시리즈 윤준서 (송승헌) 윤은서 (송혜교) 한태석 (원 빈) 한태석 (원 빈) 단풍처럼 붉게 타올랐던 <가을동화>가 낙엽이 되어 사라졌습니다. 언제 다시 그들을 만날 수 있을지 기약할 수는 없지만…...

Acute Myeloid Leukemias Proposed WHO Classification AML with recurrent cytogenetic translocations t(8;21), AML1(CBF)/ETO t(15;17), PML/RAR inv(16), CBF/MYH11 11q23(MLL) abnormalities AML with multilineage dysplasia AML and MDS, therapy related AML not otherwise categorized

Ph : der(22)t(9;22)(q34.1;q11.21) Peter C. Nowell, M.D

Practical Use of Cytogenetics in CML Advantages of Cytogentics, compared to molecular DNA studies for BCR gene rearrangement Distinguish betwn variant Ph and standard t(9;22) Dectect other abnormalities : +8, i(17q),+Ph,+19 Predict or confirm blast crisis Give information regarding percentage of normal vs abnormal cells Valuable after BMT to follow engraftment of the donor cells and identify possible relapse

MDS AML Normal Chromosome del 5q -7, del 7q del 9q del 20q +8 complex defects t(1;3), t(2;11) MDS t(3;3), inv(3) t(6;9), inv(16) t(8;21) t(9;22) t(v;11) t(15;17) AML

Myeloid Malignancy Secondary to Radiotherapy or Chemotherapy Clinical features AML-M1,M2,M6 Lower remission rate and long-term reponse Cytogenetics Usually absence of t(8;21), t(15;17) & inv(16) Usually complex karyotype Common abnormalities: -5, del(5q) in chemotherapy, -7, del(7q) in radiation therapy, Abnormalities of 3p, 11q23, 12p, and 17

José Carreras

José Carreras International Leukaemia Foundation José Carreras E. Donald Thomas Seattle's Hutchinson Clinic following a benefit concert in San Diego. Dinner party after Donald Thomas’ lecture in Kyoto

MBC 드라마 2000.12.8-9 원작 : 조창인 출연 : 정보석, 박지영 급성림프아구성백혈병 환자인 아들에게 자신의 모든 것을 희생하며 살려내는 아버지의 사랑을 그린 작품

Cytogenetics in Acute Lymphoblastic Leukemia Poorly spread, short Fuzzy chromosomes Indistinct bands Low success rate 50% in conventional culture 76% Clarkson (1985)

Ploidy Groups in Childhood ALL Hyperdiploid >50 28% Early pre-B immunophenotype Found at the age of 2-10 years Lower WBC count, Favorable prognosis Hyperdiploid 47-49 13% Diploid 46 9% Pseudodiploid 46 38% Hypodiploid <46 6%

Lymphoid Neoplasm B-Cell Neoplasm T-Cell and NK-Cell Neoplasm Proposed WHO Classification B-Cell Neoplasm Precursor B-lymphoblastic leukemia/lymphoma t(9;22), BCR/ABL t(v;11), MLL rearranged t(1;19), PBX/E2A t(12;21), ETV/CBF Mature B-cell neoplasm T-Cell and NK-Cell Neoplasm Hodgkin’s Lymphoma

Jacqueline Kennedy Onassis 1929-1994

Advance in Cancer Cytogenetics Conventional cytogenetics Molecular cytogenetics FISH (Fluorescence In Situ Hybridization) CGH (Comparative Genomic Hybridization) M-FISH(Multi-FISH, Spectral karyotyping)

Clinical Application of FISH Microdeletion syndromes Prader-Willi/Angelman syndrome DiGeorge/CATCH 22 syndrome Williams syndrome etc. Marker chromosome Hematologic malignancies t(9;22): abl/bcr t(15;17): PML/RARa 11q23: MLL t(12;21): TEL/AML1 BMT follow-up using X/Y

46,XY,t(9;22)(q34;q11.2)

Audrey Hepburn 1929-1993

Audrey Hepburn Audrey Hepburn 1929-1993

Techniques in Solid Tumor Cytogenetics 1. Preparation of tumor sample 2. Tumor cell culture Culture Media FBS (11-20%) Antibiotics Additives Tumor cells 2. Harvest 1) Colcemid (0.01-0.1mcg/ml) treatment 2) Hypotonic (0.050-0.075M KCl) treatment 3) Fixation 4) Slide preparation 3. Staining and analysis Insulin Transferrin Hydrocortisone EDGF

Cancer cytogenetics data base , reported in the five editions of “Catalog of Chromosome Aberrations in Cancer ”

Proteomics 유전체 다음 단계는 단백질 정체 규명