in vitro analysis of leukemia-specific aneuploidies by stefanie kühner

8/2/2019 In Vitro Analysis of Leukemia-specific Aneuploidies by Stefanie Khner

1/24

Gjte`cnabyna Xhiamha Hjmgatamha 0

Im wi~tj `m`cyxix jg caqlaei`%xvahigih `maqvcjiniax

im hqc~qtan bae`~jvjia~ih x~ae `mn vtjoami~jt haccx

im ~ba `dxamha `mn vtaxamha jg gjte`cnabyna arvjxqta

X~ag`mia Lbmat0# E`t~im` Xhbc`iat4# Lc`qx Xhb`t{4 `mn Om~at Xvai~0

0 Qmiwatxi~~ Qce< Imx~i~q~ gt Bqe`moama~il4 Imx~i~q~ gt Lcimixhba ^t`mxgqxijmxeani{im qmn Ieeqmoama~il "IL^)


2/24


H`thimjoamihi~y jg Gjte`cnabyna "G@)

4669*4606

^ba Im~atm`~ijm`c @oamhy gjt Taxa`thb jm H`mhat "I@TH)

ta`ggitean ~ba hc`xxigih`~ijm jg G@ im Otjqv 0

xqggihiam~ awinamha im bqe`mx jg m`xjvb`tymoa`c h`mhat

xqggihiam~ awinamha gjt caqlaei`# v`t~ihqc`tcy eyacjin caqlaei`

avinaeijcjoih`c awinamha b`x dahjea x~tjmoat-

vjxxidca eahb`mixe# imnih`~iwa jg aggah~x jm ~ba djma e`ttj-

D``m a~ `c-;C`mha~ Jmhjc- 06-# 00>8# 00>8# 00>8# 00>800>>00>>00>>00>> "4669)


3/24


4/24

Gjte`cnabyna Xhiamha Hjmgatamha >

Arvatieam~`c n`~` nj mj~ xqvvjt~ nix~`m~ xi~a "oamj%) ~jrihi~y jg G@-

G@ vtanjeim`m~cy `h~x dy hc`x~joamih ejna jg `h~ijm-

I~ ix mj~ hca`t ba~bat ~ba jdxatwan `maqvcjiniax ata `cta`ny gjtean im

~ba djma e`ttj im wiwj jt ba~bat ~bay jhhqttan nqtimo vtjcigat`~ijm im wi~tj-

I~ ix mj~ hca`t by ejmjxjey ? `mn ~tixjey 2 xbjqcn da xvahigih`ccy imnqhandy G@-

@ta ~ba jdxatwan hbtjejxjea `datt`~ijmx tac`~an ~j G@ arvjxqta:


5/24


Hqc~iw`~ijm jg bqe`m bae`~jvjia~ih vtjoami~jt haccx gjt 0> n`yx-

@m`cyxix jg 016 haccx vat xqdkah~ i~b gcqjtaxhamha im xi~q bydtinix`~ijm "GIXB)

Hjm~tjcx; 1 ! ejmjxjey ?< 6-8 ! ~tixjey 2

G@ arvjxan; 00 ! ejmjxjey ?< 0-4 ! ~tixjey 2

[b`mo a~ `c- "4606); Taxqc~x


6/24


_a hqc~iw`~an BVH im ~ba `dxamha jt vtaxamha jg G@-

_a vatgjtean GIXB `m`cyxix jg ea~`vb`xax `mn ea`xqtan `maqvcjiniax jg

hbtjejxjeax ? `mn 2-

_a imhcqnan `m`cyxix jg hbtjejxjea 7 `x ` tagatamha-

_a hb`t`h~ati{an ~ba hy~j~jrihi~y jg G@ jm hqc~qtan BVH-

@m`cyxix jg mqeatih`c hbtjejxjea `datt`~ijmx

im hqc~qtan bae`~jvjia~ih vtjoami~jt haccx "BVH)

Lqabmat a~ c-;^jrihjcjoy Xhiamhax "im vtaxx)

Nji;06-0698*~jrxhi*lgx047


7/24

Gjte`cnabyna Xhiamha Hjmgatamha ?

Bae`~jvjia~ih Hjcjmy Gjteimo @xx`y "HGQ%OE); Vtjhanqta

Dcjjn x`evcax gtje ba`c~by# yjqmo# mjm%xejlimo wjcqm~aatx-

Ixjc`~ijm jg ejmjmqhca`t haccx

"} 6-0 ! BVH im ~ba vativbat`c dcjjn)-

Ixjc`~an haccx ata eiran i~b ` xaeixjcin eaniqe hjm~`imimo

ea~bychaccqcjxa `mn w`tijqx tahjedim`m~ bqe`m otj~b g`h~jtx-

Im h`xa jg arvjxqta; G@*WHT `x `nnan nitah~cy ~j ~ba haccx-

Hqc~iw`~ijm im Va~ti nixbax gjt 9 n`yx

"8? H# 1! HJ4# 8-1! J4# =91 ! bqeini~y)-


8/24


HGQ%OE @xx`y; Vtav`t`~ijm `mn @m`cyxix

Hqc~iw`~ijm gjt 9 n`yx

Hjqm~imo jg hjcjmiax "ot`mqcjhy~ax# e`htjvb`oax)

Vtav`t ~ijm jg ea~`vb`xa xvta`nx

@m`cyxix jg 166 ea~`vb`xax vat n`~` vjim~

dy GIXB i~b vtjdax gjt hbtjejxjea 7# ? `mn 2


9/24


Taxqc~x "I); Hy~j~jrih aggah~x jg G@ jm hqc~qtan BVH

Jqt taxqc~x hjmgite ~ba hy~j~jrih aggah~ jg G@ jm hqc~qtan BVH-

6

1

06

01

46

41

Hj 46 E G@ 16 E G@ 066 E G@ 466 E G@

mqedat

jgHGQ%OE

hjcjmiaxvat066-666vc`~an

wi`dcaejmjmqhca`thaccx

+

[b`mo a~ `c- "4606)


10/24


BVH `ta mj~ v`t~ihqc`tcy xamxi~iwa ~j`tnx G@ im

hjev`tixjm i~b j~bat hqc~qtan e`ee`ci`m haccx-

Taxqc~x "II); Hy~j~jrih aggah~x jg G@ jm hqc~qtan @1>9 `mn W?9 haccx

G@ imbidi~x hcjm`c otj~b jg @1>9 mn W?9 haccx cta`ny `~ ` hjmham~t`~ijm jg 066 E-

@1>9 haccx W?9 haccx

6

46

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066

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Hj 06 E G@ 46 E G@ 16 E G@ 066 E G@ 466 E G@

mqedatjgxhjtanhjcjmiax

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+++

6

16

066

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466

416

Hj 46 E G@ 16 E G@ 066 E G@ 466 E G@

mqedatjgxhjtanhjcjmiax

++


11/24


Xieic`t d`xacima gtapqamhy jg `maqvcjin ea~`vb`xax gjt `cc ~btaa hbtjejxjeax ~ax~an-

Ejta ejmjxjeiax "6-7%6-2!) ~b`m ~tixjeiax ata ea`xqtan "6-62%6-4!)-

^ba gtapqamhy jg ejmjxjey ? `x eqhb cjat ~b`m im ~ba x~qny dy

[b`mo a~ `c- "4606)-

Taxqc~x "III); Imwax~io`~ijm jg mqeatih`c hbtjejxjea `datt`~ijmx

im hqc~qtan BVH im ~ba `dxamha jg G@

~a~t`vcjin

xqdkah~

ea~`vb`xax

xhjtan

%0 ,0 %0 ,0 %0 ,0 ea~`vb`xax

0 166 9 0 1 0 7 0 0

4 166 > 0 4 6 4 0 0

8 166 8 0 8 6 8 0 0

> 166 > 6 8 6 8 0 8

1 166 6 0 0 0 8 0 0

Ea`m XN >-6 8-4> 6-2 6->1 4-2 0->2 6-> 6-11 8-> 0-14 0-6 6-66 0-> 6-29

! 6-26 6-07 6-17 6-62 6-72 6-46 6-42

^@DCA 0

hbtjejxjea 7 hbtjejxjea ? hbtjejxjea 2

GIXB `m`cyxix jg bae`~jvjia~ih x~ae `mn vtjoami~jt haccx `g~at 9 n`yx jg hqc~qta


12/24


Taxqc~x "IW); Imwax~io`~ijm jg mqeatih`c hbtjejxjea `datt`~ijmx

im hqc~qtan BVH im ~ba vtaxamha jg G@

G@ njax mj~ imnqha `maqvcjiny qmnat ~baxa arvatieam~`c hjmni~ijmx-

Mj imhta`xa im ~ba gtapqamhiax jg `maqvcjin haccx im G@%arvjxan hqc~qtax im

hjev`tixjm i~b ~ba hjm~tjcx-

ea~`vb`xax ~a~t`vcjin

xhjtan %0 ,0 %0 ,0 %0 ,0 ea~`vb`xaxHj 0166 6-4 6-66 6-4 6-46 6-? 6-04 6-6 6-66 6-> 6-81 6-4 6#81 6-4 6-46

06 E G@ 0166 6-> 6-81 6-0 6-04 6-> 6-46 6-0 6-04 6-8 6-80 6-> 6-46 6-6 6-66

46 E G@ 0166 6-> 6-46 6-8 6-48 6-? 6-80 6-0 6-04 6-> 6-46 6-0 6-04 6-4 6-81

16 E G@ 0166 6-> 6-46 6-4 6-46 6-1 6-48 6-0 6-04 6-2 6-46 6-0 6-04 6-7 6->6

`

Ea`m XN jg ~btaa xqdkah~x-

^@DCA 4

GIXB `m`cyxix jg gjte`cnabyna%~ta`~an bae`~jvjia~ih x~ae `mn vtjoami~jt haccx \!U`

hbtjejxjea 7 hbtjejxjea ? hbtjejxjea 2


13/24


G@%~ta`~eam~ ;

Mj imnqh~ijm jg `maqvcjiny im

hqc~qtan BVH-

WHT%~ta`~eam~ ;

Imhta`xan gtapqamhiax jg

ejmjxjeiax im hqc~qtan BVH-

6-6

6-1

0-6

0-1

4-6

4-1

8-6

Hj 06 46 16

Gjte`c nabyna \EU

\!

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6

6-1

0

0-1

4

4-1

8

8-1

>

>-1ejmjxjey ~tixjey

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6-6

6-1

0-6

0-1

4-6

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Hj 6-6641 6-661

Wimhtix~ima \o*ecU

\!U

6-6

6-1

0-6

0-14-6

4-1

8-6

8-1

>-6

>-1

D

Taxqc~x "W); Imwax~io`~ijm jg mqeatih`c hbtjejxjea `datt`~ijmx

im hqc~qtan BVH im ~ba vtaxamha jg Wimhtix~im "WHT)


14/24

Gjte`cnabyna Xhiamha Hjmgatamha 0>

@ta ~baxa im wi~tj gimnimox tacaw`m~ gjt ~ba im wiwj xi~q`~ijm:

^ba dijcjoih`c EJ@ jg `maqoamx ix ~ba x`ea im wiwj `mn im wi~tj;

% mjm%NM@ ~`toa~x

% ~btaxbjcn

@maqvcjiny ix imnqhan nqtimo hacc niwixijm mn ix xaam im ea~`vb`xax

jg ~ba gjccjimo ei~jxix-

Ig `maqvcjiny ix h~q`ccy imnqhan dy G@ arvjxqta "im wiwj jt im wi~tj `~ ~ba x~`t~ jg

~ba hqc~qtax)# ~ba `maqvcjin haccx b`wa ~j xqtwiwa# vtjcigat`~a im wi~tj `mn ca`n ~j

n`qob~at haccx nqtimo xawat`c hacc niwixijmx-

_bam ~baxa tapqitaeam~x ta ea~# imhta`xan gtapqamhiax jg `maqvcjin ea~`vb`xax im

HGQ%OE hjcjmiax h`m da apq`ccy arvah~an-


15/24


Xqee`ty "I)

_a ax~`dcixban ` xamxi~iwa `mn taci`dca vtj~jhjc gjt ~ba HGQ%OE `xx`y`mn GIXB `m`cyxix jg ea~`vb`xax-

_a jd~`iman x~`dca `mn tavtjnqhidca taxqc~x-

Jqt taxqc~x xbj;

BVH `ta mj~ v`t~ihqc`tcy xamxi~iwa ~j`tnx G@-

Cjat d`xacima gtapqamhiax jg `maqvcjiniax im hqc~qtan BVH-

Mj imnqh~ijm jg `maqvcjiny dy G@ im hqc~qtan BVH-


16/24


Ix gjte`cnabyna `m `maqoam:

_a aevcjyan ~ba HDEM^ "hy~jlimaxix dcjhl eihtjmqhcaqx ~ax~);

% Ax~`dcixban x~`mn`tn oamj~jrihi~y ~ax~ gjt ~ba na~ah~ijm jg hc`x~joamih`mn `maqoamih aggah~x jg hbaeih`cx "JAHN oqinacima >2?)-

% @hhav~an gjt taoqc`~jty vqtvjxax-

_a qxan niggatam~ hacc xyx~aex "bqe`m dcjjn hqc~qtax# @1>9 haccx)-

_a na~ateiman EM gtapqamhiax im dimqhca`t haccx-

_a vatgjtean GIXB `m`cyxix jg eihtjmqhcai "EM)~j nixhtieim`~a da~aam `maqoamih `mn hc`x~joamih aggah~x-

Taxqc~x jd~ìman gjt G@ ata hjev`tan ~j aggah~x jg hjchaein `mn wimhtix~ima"i-a-# ~yvih`c `maqoamx) `mn ~j oèe`%itt`ni`~ijm "i-a-# ` ~yvih`c hc`x~joam)-

Xvai~# Lqabmat# Cimxameayat' Xhbqa~{;

Eq~òamaxix 47# 261%200 "4600)


17/24

Gjte`cnabyna Xhiamha Hjmgatamha 0?

HDEM^ im hjedim`~ijm i~b GIXB; Vtjhanqta

Hqc~iw`~ijm jg haccx

Arvjxqta ~j eq~`oamx

@nni~ijm jg Hy~jhb`c`xim D

Vtav`t`~ijm mn x~`imimo

GIXB `m`cyxix i~bv`m%ham~tjeatih vtjdax;

% ham% imnih`~ax hc`x~joamih aggah~

% ham, imnih`~ax m `maqoamih aggah~


18/24


Taxqc~x "I); @m`cyxix jg imnqhan EM im dimqhca`t bqe`m cyevbjhy~ax

6

06

46

86

>6

16

76

?6

26

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066

006

Hj 466 E G@ 866 E G@

EM\U

0-66

0-06

0-46

0-86

0->6

0-16

0-76

0-?6

0-26

0-96

4-66

HDVI

dimqhca`~an haccx

ejmjmqhca`~an haccx

HDVI

+ G@ ~ta`~eam~ im ~ba vtaxamha jg Hy~D

can ~j ` hca`t `mn hjmham~t`~ijm%tac`~an

imhta`xa im dimqhca`t haccx i~b EM-

Hy~j~jrihi~y ix imnih`~an dy ~ba tanqh~ijm

jg ~ba HDVI-


19/24


Taxqc~x "II); GIXB `m`cyxix jg imnqhan EM im dimqhca`t bqe`m cyevbjhy~ax

G@ e`imcy imnqhan ham% EM# imnih`~iwa jg ` hc`x~joamih aggah~-

^ba aggah~ jg G@ ix xieic`t ~j ~ba aggah~ jg ijmiximo%itt`ni`~ijm-

^ba maqoamx HJC mn WHT e`imcy imnqhan ham, EM- ^ba aggah~x ata hjmgitean im arvatieam~x i~b @1>9 haccx-

^`dca I- GIXB `m`cyxix jg imnqhan EM im dimqhca`t bqe`m cyevbjhy~ax`

^ta`~eam~ EM m`cy{an

ham% ham, ham% ham,

G@ "466 E) 288 >81 892 ?8-6 4?-0

G@ "866 E) 216 196 476 94-6 2-6

%t`yx "4 Oy) 0071 064? 082 98-4 7-2

HJC "6-64 o*ec) 90> 086 ?2> 1-0 91-4

WHT "6-60 o*ec) 992 46? ?90 09-4 26-2`@nnan qv gtje ~btaa arvatieam~x-

d

@g~at xqd~t`h~imo ~ba gtapqamhiax jg ham% `mn ham, jg ~ba v`t`ccac hjm~tjc-

EM Imnqhan EM \!Ud

Jqt taxqc~x arhcqna ` xiomigih`m~ `maqoamih `h~iwi~y jg G@-


20/24


Eihtj`tt`y `m`cyxix;

Oama arvtaxxijm xiom`~qta gjt hc`x~joamx `mn `maqoamx:

Haccx;

^L7 haccx "v18,)

Xqdx~`mhax; Gjte`cnabyna

4 ~yvih`c hc`x~joamx "AEX# EEX)

4 ~yvih`c maqoamx "HJC# WHT)

Arvatieam~`c naxiom;

8 imnavamnam~cy vatgjtean arvatieam~x

8 niggatam~ hjmham~t`~ijmx

4 niggatam~ ~iea vjim~x ">b# 4>b)


21/24


Ba`~ e`v;

Oama arvtaxxijm xiom`~qta gjt `maqoamx# hc`x~joamx `mn G@

Imniwinq`c v`~~atmx i~b ojjn tavtjnqhidici~y

Nix~imh~ v`~~atmx gjt `maqoamx `mn hc`x~joamx

G@ xbjx xieic`ti~iax i~b hc`x~joamx

Oama arvtaxxijm v`~~atm xaae ~j hjmgite ~ba hc`x~joamih EJ@ jg G@-

WHT

HJC

EEX

AEX

G@


22/24


Jqt taxqc~x xbj ~b`~;

G@ imnqhan EM im dimqhca`t haccx jg dj~b hacc ~yvax qmnat x~`mn`tn

im wi~tj ~ax~ hjmni~ijmx-

GIXB `m`cyxix tawa`can ~b`~ ~ba w`x~ e`kjti~y jg imnqhan EM ata ham%#

~bqx imnih`~imo ` hc`x~joamih aggah~-

Jqt taxqc~x hjmgite ~ba hc`x~joamihi~y jg G@ im hqc~qtan e`ee`ci`m haccx

dq~ arhcqna ` xiomigih`m~ `maqoamih `h~iwi~y-

Eihtj`tt`y m`cyxix xqvvjt~ hc`x~joamih EJ@-

Xqee`ty "II)


23/24


Hjmhcqxijmx

Jqt x~qny nin mj~ gimn imnih`~ijmx gjt ` vj~am~i`c jg G@ ~j imnqha maqvcjiny-

Jqt taxqc~x pqax~ijm m maqoamih aggah~ jg G@ jm BVH x vj~am~i`c eahb`mixe

gjt ~ba imnqh~ijm jg caqlaei`-

^ba hjmxinat`~ijm jg xqhb ` eahb`mixe dy I@TH xaaex ~j da xhiam~igih`ccy

qmkqx~igian `mn vtae`~qta-


24/24

Gjte`cnabyna Xhiamha Hjmgatamha 4>

Xvahi`c ~b`mlx ~j;

Om~at Xvai~

E`t~im` Xhbc`iat

Lc`qx Xhb`t{

Gqmnimo; Aqtjva`m Hbaeih`c Imnqx~ty Hjqmhic

"HAGIH*Gjte`H`ta)

in vitro analysis of leukemia-specific aneuploidies by stefanie kühner

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