Acute Myeloid Leukemia (AML)

JAX® MICE, CLINICAL & RESEARCH SERVICES
Acute Myeloid Leukemia (AML)
MODELING HUMAN LEUKEMIA IN AN IMMUNODEFICIENT MOUSE
A patient-derived
xenograft resource
AML models
•Best in class immunodeficient mouse,
NOD scid IL2 receptor gamma chain knockout (NSG) as the host
Clinical history
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•
•
•
Blast phenotype
partial CD4, partial CD7, CD13, partial CD15, CD33, partial
CD64, CD117, and HLA-DR
Diagnosis:
FAB-NOS
Karyotype
46 XY
AML FISH panel
negative
Molecular profile
Multiplex mutation screening* shows
1) IDH1 exon 2 R132H
2) NPM1 exon 12 W288fs
Engraftment
in NSG mice
6-10% of AML engraftment and absence of T cells in the
peripheral blood 24 weeks post injection.
TM01505 (IDH1 slow)
•Engraftment of the leukapheresed AML samples in the NSG mice has been confirmed
•Average time to confirm AML engraftment in the peripheral blood of NSG mice is
10-16 weeks post injection
•Client sponsored efficacy studies can be executed by JAX® In Vivo Pharmacology
Service group
•Engrafted mice can be delivered to
client site
•Supplies are limited, models are available
first come, first serve
FAQ Questions
TM01595 (IDH1 fast)
Clinical history
•
•
•
•
Blast phenotype
CD11b, CD13, variable CD14, variable CD15, dim CD16, CD33,
CD56, CD64, CD123, partial CD117, and HLA-DR positive
Diagnosis:
FAB-M5
Karyotype
46 XY
AML FISH panel
negative
Molecular profile
Multiplex mutation screening* shows
• IDH1 exon 2 R132H
• NPM1 exon 12 W288fs
• NRAS exon 2 Q61H
Engraftment
in NSG mice
6-10% AML cells in peripheral blood 12 weeks post injection,
death around 20 weeks post injection.
Tested for engraftment?
All models have been confirmed to engraft in the NSG mice
How many mice can be engrafted from one
AML sample?
Approximately 400-4,000 mice per AML model
Enough mice to support longitudinal studies
from the same AML sample?
Yes (FAQ continued on back)
1.800.422.6423
1.207.288.5845
FS0136 4/24/2014
Age: 38
Sex: Male
WBC: 80,000 at diagnosis
Leukapheresis secondary to visual loss and soft tissue
infiltration of the upper airway. Achieved a complete
response (CR) with 3+7 induction therapy then completed
4 cycles of HiDAC consolidation. Relapsed 32 months
after diagnosis, achieved a second CR then underwent an
allotransplant. Currently in remission.
www.jax.org/jaxservices/invivo/pdx/aml
[email protected]
Age 37
Sex Male
WBC 109,400 at diagnosis
Airway impingement requiring tracheotomy at diagnosis.
Complete response with 3+7 but relapsed at 3 months. Two
cycles of salvage therapy administered, but the patient died
of refractory AML at 8 months post diagnosis.
AML MODELS
(FAQ continued from front)
Molecular Profile?
Two models are FLT3 ITD mutants and two models are IDH1 mutants.
Spare samples to test the presence of
my biomarker?
Yes
What engraftment levels do you typically see?
0~30% AML in the peripheral blood of
NSG mice 10-26 weeks post engraftment.
Take rates on peripheral blood and
bone marrow?
>95%
AML models
TM00347 (FLT3 ITD fast)
Clinical history
•
•
•
•
Blast phenotype
partial CD34, CD117, partial CD4,
partial CD11b, 13, CD33, HLA- DR+
Diagnosis
FAB-M2
Karyotype
46 XY
AML FISH panel
negative
Molecular profile
Flt3-ITD positive. Multiplex mutation screening
shows *NPM1 exon 12 insertion mutation (W288fs).
Engraftment
in NSG mice
High level of AML engraftment (~30%) and absence
of T cells in peripheral blood 9 weeks post injection.
Death around 20 weeks post engraftment.
Age: 52
Sex: Male
WBC: 293, 000 at diagnosis
Died of cardiopulmonary arrest within
48 hours of admission to hospital.
Do mice die from this cancer?
Death around 20 weeks post engraftment
for TM00347 and TM01595.
TM00346 (FLT3 ITD slow)
Clinical history
•
•
•
•
Blast phenotype
dim CD4, partial CD7, CD11b, CD13,
partial CD22, CD33, CD34, CD117
and HLA-DR
Diagnosis
FAB-M2
Karyotype
46 XY
AML FISH panel
negative
Molecular profile
Flt3-ITD positive. Multiplex mutation screening*
shows no additional mutations.
Engraftment
in NSG mice
High level of AML engraftment (~20%) and absence
of T cells in peripheral blood 16 weeks post injection
Age: 22
Sex: Male
WBC: 405,000 at diagnosis
Aggressive disease that required
2 cycles of induction chemotherapy. Relapsed
within 2 months and died
of refractory AML within 6 months
of diagnosis.
* Multiplex mutation screening: includes 344 point mutations in
the following 31 genes: ABL AKT1 AKT2 AKT3 BRAF CBL CBLB
FBXW7 FES FGFR4 FLT3* FMS GATA1 HRAS IDH1 IDH2 JAK1
JAK2 JAK3 KIT KRAS MET MPL NOTCH1 NPM1 NRAS NTRK1
PAX5 PDGFRB PTPN11 SOS1 (*FLT3 gene-point mutations only,
additional assay required for ITD)
1.800.422.6423
1.207.288.5845
FS0136 4/24/2014
www.jax.org/jaxservices/invivo/pdx/aml
[email protected]

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