27 lncrnas (predictive of subtype) 10 lncrnas (ts & onc.) 8 lncrnas 4 lncrnas (balr-1, balr-2,...

27 lncRNAs(predictive of subtype)

10 lncRNAs(TS & Onc.)

8 lncRNAs

4 lncRNAs(BALR-1, BALR-2,

BALR-6, LINC00958)

114 lncRNAs

2 lncRNAs(BALR-2, BALR-6)

Microarray

Nearest shrunken centroid analysis

81 lncRNAs

Expression in leukemia > or < than pro-B cells

17 lncRNAs

GenBank ESTs and mRNAs

Available transcript models

2 lncRNAs

Expression >in leukemic samples

4 lncRNAs(TS)

FC > 2 adj. p < 0.01

Clinicopathologicalparameters

2 lncRNAs

BALR-2

Prednisone responseSubcellular localization

Futurestudies

Supplemental Figure 1

c

e f

a

d

bM

iscl

ass

ifica

tion

Err

or

Value of Threshold

0.8

0.2

0.4

0.6

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

Number of genes

miss

class

ifica

tion

erro

r

Value of Threshold

1112

4Number of Genes

2 4 6 8 10 12

6886

1


Value of Threshold

Mis

cla

ssifi

catio

n E

rro

rNumber of Genes

2596

322

099

1377

368

8635

6219

3811

1266

237

824

116

511

376 54 41 31 25 20 17 11 9 6 4 4 3 2 2 1 1 0

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

Number of genes

Miss

clas

sifica

tion

erro

r

Value of threshold

ALL1

ALL2

ALL3

Number of genes

2 4 6 8 10 12

0.8

0.2

0.4

0.668

8611

12

4 1

TEL-AML1E2A-PBXMLL

Number of lincRNAs

Mis

cla

ssifi

catio

n E

rro

r

7419

7002

5832

4345

2887

1791

1022

618

389

249

168

123

87 62 50 34 27 18 15 14 12 11 8 7 6 6 4 4 3 0

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0

0.24

6

0.49

2

0.73

9

0.98

5

1.23

1

1.47

7

1.72

3

1.97

2.21

6

2.46

2

2.70

8

2.95

4

3.2

3.44

7

3.69

3

3.93

9

4.18

5

4.43

1

4.67

8

4.92

4

5.17

5.41

6

5.66

2

5.90

9

6.15

5

6.40

1

6.64

7

6.89

3

0.8

0.2

0.4

0.6

2 4 6Value of Threshold

27618

44345

TEL-AML1E2A-PBXMLL

Value of Threshold

7419 7002 5832 4345 2887 1791 1022 618 389 249 168 123 87 62 50 34 27 18 15 14 12 11 8 7 6 6 4 4 3 0

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

Mis

cla

ssifi

catio

n E

rro

r

2 4 6

27 4

Number of lincRNAs

0.8

0.2

0.4

0.6

618

4345

ALL Cases

0.2

0.6

1

00 5 10 15 20 25

TEL-AML1E2A-PBXMLL

ALL Cases

0

0.2

0.6

1

0 5 10 15 20 25

Pro

ba

bili

ty o

f co

rre

ct

cla

ssifi

catio

n

Pro

ba

bili

ty o

f co

rre

ct c

lass

ifica

tion TEL-AML1

E2A-PBXMLL

0

5000

10000

15000

20000

25000

30000

0 2 4 6 8 10 12 14

Threshold

Nu

mb

er

of

ge

ne

s

01000

2000

3000

4000

5000

6000

7000

8000

0 1 2 3 4 5 6 7 8

Threshold

Nu

mb

er

of

lincR

NA

g h

a b

c d

e f

g


Time (days)

Cu

mu

lati

ve

Su

rviv

al

0 100 300 500

1.0

0.6

0.2

0

0.8

0.4

High BALR-6

Low BALR-6

Time (days)

Cu

mu

lati

ve

Su

rviv

al

0 100 300 500

1.0

0.6

0.2

0

0.8

0.4

High BALR-1

Low BALR-1

Time (days)

Cu

mu

lati

ve

Su

rviv

al

0 100 300 500

1.0

0.6

0.2

0

0.8

0.4

High LINC00958

Low LINC00958

BALR-2

Fre

qu

en

cy

40

10

0

30

20

0 0.2 0.4 0.6 0.8

LINC00958F

req

ue

nc

y

30

10

0

20

0 1.0 10.0 100.0

BALR-1F

req

ue

nc

y50

10

0

40

30

0 1.0 10.0

20

BALR-6

Fre

qu

en

cy

15

10

0

0 1.0 10.0 100.0 1000.0

5

RASSF10

LINC0095811q15.2

mRNA: NR_038904

Probe set on microarray

qPCR primers

TEAD1

RACE product

LOC100506305

BALR-63p24.3

mRNA: NM_001257177

Probe set on microarray

qPCR primers

LOC339862 SATB1TBC1D5

RACE product

14q32.2

C14orf132

mRNA: NM_001252507

Probe seton microarray

qPCR primers

LINC00617 BDKRB2

BALR-1a b

c


BALR-2

5’ RACE product 1

3’ RACE product

5’ RACE primerUn-annotated exon

AAAAA

5’ RACE product 2

5’ RACE product 3

80kb

Balr-2

3’ RACE product 1

3’ RACE primer

3’ RACE product 2

d

e

5’ RACE 3’ RACE1000 bp

500 bp

1000 bp

500 bp

3’ RACE NC

VECTOR

siRNA 2

0.0

0.5

1.0

1.5

BA

LR

-2(f

old

Ch

ang

e) **

VECTOR

siRNA 2

0

5

10

15

FO

S(f

old

ch

ang

e) **

VECTOR

siRNA 2

0

2

4

6

8JU

N(f

old

ch

ang

e)**


VECTOR

siRNA2

0.0

0.5

1.0

1.5

2.0

2.5

SG

K1

(fol

d c

han

ge)

*

VECTOR

siRNA2

0

1

2

3

4

5

SE

RP

INE

1(f

old

ch

ang

e) **

f g

h

FO

S(f

old

ch

ang

e)

UNT

PRED

DEXADOX

UNT

PRED

DEXADOX

0

5

10

15RS4;11NALM-6*** **

p=0.06**

**

*

JUN

(fol

d c

han

ge)

UNT

PRED

DEXADOX

UNT

PRED

DEXADOX

0

5

10

15

20RS4;11NALM-6

******

******

**

****

BIM

(fol

d c

han

ge)

UNT

PRED

DEXADOX

UNT

PRED

DEXADOX

0

2

4

6

8RS4;11NALM-6**

***

***

**

*

a b c

d e

VECTOR

sispli

ce1

0.0

0.5

1.0

1.5

BA

LR

-2(f

old

ch

ang

e) ***

VECTOR

sispli

ce1

0.00

0.05

0.10

0.15

0.20

casp

ase-

3 a

ctiv

ity (

A4

05)

*

VECTOR

siRNA3

0.0

0.5

1.0

1.5

BA

LR

-2(f

old

ch

ang

e) **

VECTOR

siRNA3

0.00

0.01

0.02

0.03

0.04

0.05

Cas

pas

e-3

act

ivity

(A

40

5)

*

fold

ch

ang

e

VECTOR

siRNA3

VECTOR

siRNA3

0.0

0.5

1.0

1.5

2.0

2.5FOSJUN

p = 0.09

*

VECTOR

siRNA3

0.0

0.5

1.0

1.5

BA

LR

-2(f

old

ch

ang

e) **

fold

ch

ang

e

VECTOR

sispli

ce1

VECTOR

sispli

ce1

VECTOR

sispli

ce1

0

5

10

15FOSJUN

p = 0.07

***BIM

***

fold

ch

ang

e

VECTOR

siRNA3

VECTOR

siRNA3

0.0

0.5

1.0

1.5

2.0FOSJUN

**

**

BA

LR-2

(fold

cha

nge)

0.0

0.5

1.0

1.5F

old

Ch

ang

e

VECTOR

siRNA1

siRNA2

siRNA3

VECTOR

siRNA1

siRNA2

siRNA3

VECTOR

siRNA1

siRNA2

siRNA3

0

1

2

3

4

5FOSJUNBIM

p=0.06

p=0.07

***

** *

Time (hours)

cell

pro

lifer

atio

n(f

old

ch

ang

e)

0 24 48 72 960

2

4

6

8

10

12

14

VECTORsiRNA1siRNA2siRNA3


% o

f apo

ptot

ic c

ells

0

5

10

15

20 125 g/mL250 g/mL

*

**

**

VECTOR

siRNA3

0

5

10

15

20

25

% a

pop

totic

cel

ls *

a b c

d

e f g

h i j

k l m


PRED

GR

BIM

BALR-2

JUN JUN

FOS

Cytokines/survival genes

?

Caspase-3 APOPTOSIS

FOS

27 lncrnas (predictive of subtype) 10 lncrnas (ts & onc.) 8 lncrnas 4 lncrnas (balr-1, balr-2,...

Documents

high balr

low balr

race primer3 race product

abcsupplemental figure

racenc4 supplemental

time dayscumulative

fgh abcde supplemental

junfoscytokinessurvival