Molecular cytogenetics in hematologic malignancy
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혈액종양의 분자세포유전학 Molecular Cytogenetics in hematologic Malignancy - PowerPoint PPT Presentation

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혈액종양의 분자세포유전학 Molecular Cytogenetics in hematologic Malignancy. Historical Backgroud. Philadelphia chromosome (Ph) 1970 Banding technique 1970 t(9;22) in CML 1973 t(8;21) in AML-M2 t(8;14) in Burkitt lymphoma/Leukemia 1977 t(15;17) in AML-M3, t(4;11)

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혈액종양의 분자세포유전학 Molecular Cytogenetics in hematologic Malignancy

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혈액종양의 분자세포유전학Molecular Cytogenetics in hematologic Malignancy

Historical Backgroud

  • Philadelphia chromosome (Ph)

  • 1970Banding technique

  • 1970 t(9;22)in CML

  • 1973 t(8;21)in AML-M2

  • t(8;14)in Burkitt lymphoma/Leukemia

  • 1977 t(15;17)in AML-M3, t(4;11)

  • 1979 High-resolution banding technique

  • 1980

  • 1982t(9;11) in AML-M5a, inv(3) in AML

  • 1983 inv(16) in AML-M4E

  • 1984 t(1;19) in ALL

  • t(1;3) in AML with dysmegakaryopoiesis

  • 1990 Molecular cytogenetics (FISH, CGH)

Cytogenetic & Gene Rearrangement

  • 1980

  • 1983 MYC-IGH t(8;14)

  • 1984 BCR-ABL1 t(9;22)

  • IGH-BCL2 t(14;18)

  • 1990

  • 1991 MLL-AFF1 t(4;11)

  • E2A-PBX1 t(1;19)

  • PML-RARA t(15;17)

  • RUNX1-RUNX1T1 t(8;21)

  • DEK-NUP214 t(6;9)

  • 1993 CBFB-MYH11 inv(16)

  • MLL-MLLT3 t(9;11)

  • 1997 TEL-AML1t(12;22)

KimSW, et al.: Banding patterns of normal human chromosomes. The Seoul Journal of Medicine 21(2):133-137(1980).

Cytogenetic Studies for Hematologic Malignancies in Korea

Table 4. Karyotypic pattern in cases with CML

조혈기질환에 있어서 골수세포

염색체 분석에 관한 연구.

대한혈액학회지 23(2),1988

Leukemia in Cinema



안녕 내사랑

태양은 가득히

Last Concert

Love Story

Dying Young

Marvin’s Room

Roman Holiday

Love means never

having to say you're sorry


Ali MacGraw (Jeniffer)

Ryan O'Neal (Oliver)

Music (Snow Frolic)

Francis Lai

Written by Erich Segal (1970)

Philadelphia Chromosome (=Ph) der(22)t(9;22)(q34.1;q11.21)





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.


CML Blast Crisis - Karyotype

Practical Use of Cytogenetics in CML

  • Advantages ofCytogentics, compared to molecular DNA studiesfor 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

Richard Johnson

Pamela Villoresi

Stelvio Cipriani

Dedicato A Una Stella

1976, Italy

불치 병(백혈병)에 걸린 아가씨와 오랜 슬럼프에 빠진 피아니스트의 슬픈 사랑을 엮은 러브스토리

APL with t(15;17)(q22;q21), PML/RARA

From highly fatal to highly curable




ATRA (all-trans retinoic acid)

& ATO (arsenic trioxide)

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

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




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.

KBS 미니시리즈


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)

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

Normal Chromosome

del 5q

-7, del 7q

del 9q

del 20q


complex defects

t(1;3), t(2;11)


t(3;3), inv(3)

t(6;9), inv(16)






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 E. Donnall

Thomas’ lecture in Kyoto (1991)

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 >5028%

    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 4638%

  • Hypodiploid <46 6%

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

Jacqueline Kennedy Onassis


Cytogenetics Technologies


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


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.

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


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

Audrey Hepburn


Solid Tumor Cytogenetics

1. Preparation of tumor sample

2. Tumor cell culture

Culture Media

FBS (11-20%)



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





Solid Tumor Abnormalities

“Catalog of Chromosome Aberrations in Cancer ”

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