1. 혈액종양의 분자세포유전학 Molecular Cytogenetics in hematologic Malignancy

2. Historical Backgroud Philadelphia chromosome (Ph)
Banding technique
t(9;22) in CML
t(8;21) in AML-M2
t(8;14) in Burkitt lymphoma/Leukemia
t(15;17) in AML-M3, t(4;11)
High-resolution banding technique
1980
t(9;11) in AML-M5a, inv(3) in AML
inv(16) in AML-M4E
t(1;19) in ALL
t(1;3) in AML with dysmegakaryopoiesis
Molecular cytogenetics (FISH, CGH)

3. Cytogenetic & Gene Rearrangement
1980
MYC-IGH t(8;14)
BCR-ABL1 t(9;22)
IGH-BCL2 t(14;18)
1990
MLL-AFF1 t(4;11)
E2A-PBX1 t(1;19)
PML-RARA t(15;17)
RUNX1-RUNX1T1 t(8;21)
DEK-NUP t(6;9)
CBFB-MYH inv(16)
MLL-MLLT t(9;11)
TEL-AML t(12;22)

4. Cytogenetic Studies for Hematologic Malignancies in Korea
Table 4. Karyotypic pattern in cases with CML
Karyotype
No.
t(22q;9q) 7
22q- 6
22q-. -9 1
49,XXX,+9,+21
Normal 21
조혈기질환에 있어서 골수세포
염색체 분석에 관한 연구.
대한혈액학회지 23(2),1988
KimSW, et al.: Banding patterns of normal human chromosomes. The Seoul Journal of Medicine 21(2): (1980).

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

6. having to say you're sorry
Love means never
having to say you're sorry
Starring
Ali MacGraw (Jeniffer)
Ryan O'Neal (Oliver)
Music (Snow Frolic)
Francis Lai
Written by Erich Segal (1970)

7. Philadelphia Chromosome (=Ph) der(22)t(9;22)(q34.1;q11.21)
BCR
q34
ABL
Ph (formerly Ph1) may be used in text, but not in the description of the karyotype, where der(22)t(9;22)(q34;q11.2) is recommended.

8. 50,XX,+8,t(9;22)(q34;q11.2),+10,+19, +der(22)t(9;22)(q34.1;q11.21)
CML Blast Crisis - Karyotype
50,XX,+8,t(9;22)(q34;q11.2),+10,+19, +der(22)t(9;22)(q34.1;q11.21)

9. 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

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

11. APL with t(15;17)(q22;q21), PML/RARA
From highly fatal to highly curable
RARA
PML
PML/RARA
G-banding : t(15;17)(q22;q21) & Variants of t(15;Var;17), t(11;17), t(5;17) RT-PCR, FISH : PML/RARA fusion transcript
ATRA (all-trans retinoic acid)
& ATO (arsenic trioxide) 11

12. 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

13. 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.

14. KBS 미니시리즈
가을동화
극중의 의사는 은서가 백혈병에 걸린 사실을 확인하는 과정에서 ‘유전이 될 확률이 높은 병’이라고 말하는데…… 하지만 백혈병이 유전되는 병은 아니다.
윤준서 (송승헌)
윤은서 (송혜교)
한태석 (원 빈)

15. Acute Myeloid Leukemia and Related Neoplasms
Proposed WHO Classification
AML with recurrent genetic abnormalities
t(8;21), RUNX1-RUNX1T1
t(15;17), PML/RAR
inv(16), CBF/MYH11
t(9;11), MLLT3/MLL
t(6;9), DEK/NUP214 
inv(3) or t(3;3), RPN1-EVI1 
t(1;22), RBM15-MKL1 
Acute myeloid leukemia with myelodysplasia-related changes
Therapy-related myeloid neoplasms
Acute myeloid leukemia, not otherwise specified
Myeloid sarcoma
Myeloid proliferations related to Down syndrome
Blastic plasmacytoid dendritic cell neoplasm

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 E. Donnall
Thomas’ lecture in Kyoto (1991)

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. Precursor Lymphoid Neoplasm
Proposed WHO Classification
B lymphoblastic leukemia/lymphoma, NOS
B lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities
t(9;22)(q34;q11.2); BCR-ABL1
t(v;11q23); MLL rearranged
t(12;21)(p13;q22) TEL-AML1 (ETV6-RUNX1)
hyperdiploidy
hypodiploidy
t(5;14)(q31;q32) IL3-IGH
t(1;19)(q23;p13.3);TCF3-PBX1
T lymphoblastic leukemia/lymphoma

24. Jacqueline Kennedy Onassis

25. Cytogenetics Technologies
Karyotyping
Provides a visual examination of the entire genome
the best coverage but not the best resolution (≥ 5 Mb)
Banding resolution differs from preparation to preparation
FISH
Sensitive (high resolution)
Only provides information on tested regions, other aberrations will NOT be tested, i.e. not genome view
M-FISH(Multi-FISH, Spectral karyotyping)
Array-based Copy Number / CGH Analysis
Single step global genome scan prevents FISHing expedition
BAC (Bacterial Artificial Chromosome) Array
Requires well characterized and high resolution clones
High Resolution Oligonucleotide Microarray
Highest resolution.
Precise identification of gains and losses of genetic material. 25

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. "Remember you another hand
"Remember you another hand. The first is to help yourself, the second is to help others."
Audrey Hepburn

29. 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

30. Solid Tumor Abnormalities
der(1)
breast carcinomas
del(1p)
colorectal adenoma
del(3)(p12p14)
del(3)(p14p23)
small cell carcinoma of lungs
del(3p)
renal cell carcinoma,
non-small cell lung cancer
del(7)(q21q31)
uterine leiomyomas
del(9)(p13)
malignant melanoma
del (11)(p13)
Wilm's tumor
del(22q) or -22
meningiomas
i(6)(p10)
retinoblastoma
i(8)(q10)
uveal melanoma
i(12)(p10)
testicular germ cell tumors
i(17)(q10)
primitive neuroectodermal tumor
inv(10)(q11q21)
papillary carcimoma of the thyroid
t(1;17)(p36;q12)
neuroblastoma

31. inv(10)(q11q21)
papillary carcimoma of the thyroid
t(1;17)(p36;q12)
neuroblastoma
t(2;13)(q35;q14)
alveolar rhabdomyosarcoma
t(3;8)(p21;q12)
pleomorphic ademoma of salivary glands
t(3;12)(q27-28;q13-15)
sporadic typical lipomas
t(9;22)(q22;q11-12)
extraskeletal myxoidchondrosarcoma
t(11;19)(q21;p11)
mucoepidermoid carcinoma,
adenolymphoma of salivary gland
t(11;22)(p13;q12)
intraabdominal desmoplastic small round cell tumor
t(11;22)(q24;q12)
Askins tumor,
Ewings sarcoma, esthesioneuroblastoma
t(12;14)(q14-15;q23-24)
uterine leiomyomas
t(12;16)(q13;p11.2)
myxoid liposarcoma
t(X;1)(p11;q21)
malignant papillary renal cell carcinoma
t(X;18)(p11.2;q11.2)
synovial sarcoma

34. “Catalog of Chromosome Aberrations in Cancer ”