혈액종양의 분자세포유전학 Molecular Cytogenetics in hematologic Malignancy

Presentation on theme: "혈액종양의 분자세포유전학 Molecular Cytogenetics in hematologic Malignancy"— Presentation transcript:

1 혈액종양의 분자세포유전학 Molecular Cytogenetics in hematologic Malignancy

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

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

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

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

6 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

7 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

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

9 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

10 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.

11 장호태 (박상민) 강민기 (유준상) 박지숙 (김지수)
KBS 2TV 주말연속극 장호태 (박상민) 강민기 (유준상) 박지숙 (김지수) 강한 태양(인간의 욕망)은 강한 그림자를 남긴다

12 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…...

13 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

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

15 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

16 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

17 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

18 José Carreras

19 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

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

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

22 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 % Diploid % Pseudodiploid % Hypodiploid < %

23 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

24 Jacqueline Kennedy Onassis

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

26 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

27 46,XY,t(9;22)(q34;q11.2)

28

29 Audrey Hepburn

30 Audrey Hepburn Audrey Hepburn

31 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 ( mcg/ml) treatment 2) Hypotonic ( M KCl) treatment 3) Fixation 4) Slide preparation 3. Staining and analysis Insulin Transferrin Hydrocortisone EDGF

32

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

34 Proteomics 유전체 다음 단계는 단백질 정체 규명