Angiogenesis in Multiple Myeloma

Angiogenesis in Multiple Myeloma
S. Vincent Rajkumar, MD
Associate Professor of Medicine
Mayo Clinic
Rochester, Minnesota

Myeloma Angiogenesis: CD34
Rajkumar & Greipp Br J Hematol 2001; 113:565

1.0
0.8
P = 0.004 (Wilcoxon)
0.6
MVD <50
Probability
0.4
MVD >50
0.2
0.0
24
6
8
10
Years
Rajkumar, Clin Cancer Res 2000; 6:3111-3116

Kyle RA and Rajkumar SV. N Engl J Med 2004;351:1860-73

50
40
30
MVD
20
P<0.001
10
0
NAL MGUS SM MM RMM
MVD in Plasma Cell Disorders
Rajkumar, Clin Cancer Res 2002

Angiogenesis in PC Disorders: CD34
Rajkumar, Clin Cancer Res 2002

Angiogenesis and PCLI
10
8
PCLI
6
P<0.001
(%)
4
2
0
Low
Intermediate
High
Angiogenesis Grade Rajkumar, Clin Cancer Res 2002

Vacca et al. Blood 1999;93:3064-73

VEGF by ELISA
4000
3000
L
Supernatant
/m 2000
pg
Lysate
1000
0
ANBL-6
KP-6
KAS6/1
OPM2
8226
OCI-My5
RPMI
Cel lines
Rajkumar, Leukemia 2003

VEGF Expression in myeloma by RT-PCR
8
5
6
2
5
H9
Y
2
6
-6
2
5
266
0
M
KAS
8
KP6
2
CESS
K
U
RNA
AR
ANBL
M0
No
541 bp
408 bp
1
2
3
4
5
Patient
Patient
Patient
Patient
Patient
541 bp
408 bp
Rajkumar, Leukemia 2003

Giuliani N et al. Blood 2003;102:638-645

Flt-1 Expression in myeloma by nested RT-PCR
9
6
5
S
2
6
-6
A
H
Y
6
AS
22
L
N
R
2
K
8
KP6
ES
56
B
R
A
M
C
K
N
U
o
A
N
541 bp
1
2
3
4
t
5
C
t
n
t
E
n
n
tie
tie
tie
UV
a
a
a
H
Patient
P
P
P
Patient
541 bp
Rajkumar, Leukemia 2003

KDR Expression in myeloma by nested RT-PCR
6
6
85
A
H9
-6
AS
22
L
0
N
KP6
B
26
2
R
AR
MY5
K
8
CESS
K562
N
U
0
A
M
oN
500 bp
1
2
3
4
5
C
t
t
t
t
t
E
n
n
n
n
n
tie
tie
tie
tiea
tie
HUV
a
a
a
a
P
P
P
P
P
500 bp
Rajkumar, Leukemia 2003

Kumar et al, Blood 2004; 104:1159-1165

Giuliani N et al. Blood 2003;102:638-645

Vacca et al. Blood 1999;93:3064-73

Kumar S et al. Blood 2004;104:1159-1165

Kumar et al, Blood 2004; 104:1159-1165

Solitary Plasmacytoma
1
0.8
High Grade
0.6
Survival
Low Grade
Censor Times
0.4
Cum.
0.2
0
0
50 100 150 200 250 300 350 400
Time (months)
Kumar S, Blood 2003

Myeloma-Endothelial Cell
Interactions
Growth, Proliferation
PTK787
Myeloma cells
Endothelial cells
Dankbar, Blood 2001; Podar, Blood 2001; Gupta, Blood 2001

MM1.S
HUVEC
HUVEC+MM1.S
350000
300000
250000
200000
m
cp 150000
100000
50000
0
02
48
12
16
20
24
Huvec number (X1000)
Kumar S.

Vacca A et al. Blood 2003;102:3340-3348

Zhang H et al. Blood 2005;105:3286-3294

Response, TTP
NIH
R01
JAX
9
5
S
6
6
S
2
6
8
A
Y
2
S
6
-6
6
5
2
5
L
0
N
2
M
KA
8
KP
CE
K
U2
R
ARH
ANB
M0
No
Thal + ZA
541 b p
vs
ROC
408 b p
ZA
SCO
VEGF
t1
t2
n
n
t3
t4
t5
e
e
n
n
n
e
e
e
ati
ati
ati
ati
ati
P
P
P
P
P
541 b p
408 b p
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