| |
Section
II: Patient Dataset
A total of 389 Pediatric acute leukemia
samples were analyzed in this study, from which high quality
gene expression data were obtained on 360 (93%). The successfully
analyzed samples included: 332 diagnostic bone marrows (BM),
3 diagnostic peripheral bloods (PB), and 25 relapse ALL
samples from BM or PB. 264 (79%) of the diagnostic ALL BM
samples and all relapse samples were from patients treated
on St. Jude Children's Research Hospital Total Therapy Studies
XIIIA or XIIIB and correspond to 64% of the patients treated
on these protocols. The details of these protocols have
been previously published. 1,2 XIIIA ran from
12-20-91 to 8-23-94 and enrolled 165 patients, whereas XIIIB
ran from 8-24-94 to 7-27-98 and enrolled 247 patients. No
patients were lost to follow-up during treatment. When the
databases were frozen for analysis, 100% and 93% of event-free
survivors in studies XIIIA and XIIIB, respectively, had
been seen within 12 months. The median (minimum, maximum)
follow-up of the event-free survivors was 8.09 (6.59, 9.94)
and 4.52 (2.37, 7.06) years for XIIIA and XIIIB, respectively.
All other samples were obtained from patients treated on
St. Jude Total Therapy Studies XI, XII, XIV, XV, or by best
clinical management.
For the identification of gene expression profiles that predict specific
genetic subtypes of ALL, 327 diagnostic BM samples were used. Inclusion
in this dataset required availability of a cryopreserved diagnostic BM
sample containing >75% blasts, and complete data from each
of the following diagnostic studies: morphology, immunophenotype, cytogenetics,
DNA ploidy, Southern blot for MLL gene rearrangements, and RT-PCR analysis
for MLL-AF4, MLL-AF9, E2A-PBX1, TEL-AML1,
and BCR-ABL. This final dataset includes diagnostic BM samples
from XV (38), XIV (4), XIIIA (100), XIIIB (161), or from patients treated
on one of our older protocols or by best clinical management (24).
The data sets used to identify expression profiles predicative of hematologic
relapse and the development of therapy-induced AML are described below.
Table 10. Patient database
|
| Diagnostic
samples used for subtype classification (n=327) |
|
|
BCR-ABL subgroup (n=15)
|
|
Label@
|
Protocol#
|
Outcome%
|
|
Label@
|
Protocol#
|
Outcome%
|
|
BCR-ABL-C1
|
T13B
|
CCR
|
|
BCR-ABL-#4
|
T11
|
NA
|
|
BCR-ABL-R1
|
T13A
|
Heme Relapse
|
|
BCR-ABL-#5
|
T12
|
NA
|
|
BCR-ABL-R2
|
T13A
|
Heme Relapse
|
|
BCR-ABL-#6
|
T12
|
NA
|
|
BCR-ABL-R3
|
T13B
|
Heme Relapse
|
|
BCR-ABL-#7
|
T12
|
NA
|
|
BCR-ABL-Hyperdip-R5
|
T13B
|
Heme Relapse
|
|
BCR-ABL-#8
|
T14
|
NA
|
|
BCR-ABL-#1
|
T13A
|
Censored
|
|
BCR-ABL-#9
|
T15
|
NA
|
|
BCR-ABL-#2
|
T13B
|
Censored
|
|
BCR-ABL-Hyperdip-#10
|
T12
|
NA
|
|
BCR-ABL-#3
|
T13B
|
Censored
|
|
|
|
|
| |
|
|
|
|
|
|
E2A-PBX1 subgroup
(n=27)
|
|
E2A-PBX1-C1
|
T13A
|
CCR
|
|
E2A-PBX1-#1
|
Others
|
NA
|
|
E2A-PBX1-C2
|
T13A
|
CCR
|
|
E2A-PBX1-#2
|
Others
|
NA
|
|
E2A-PBX1-C3
|
T13A
|
CCR
|
|
E2A-PBX1-#3
|
Others
|
NA
|
|
E2A-PBX1-C4
|
T13A
|
CCR
|
|
E2A-PBX1-#4
|
Others
|
NA
|
|
E2A-PBX1-C5
|
T13A
|
CCR
|
|
E2A-PBX1-#5
|
Others
|
NA
|
|
E2A-PBX1-C6
|
T13B
|
CCR
|
|
E2A-PBX1-#6
|
Others
|
NA
|
|
E2A-PBX1-C7
|
T13B
|
CCR
|
|
E2A-PBX1-#7
|
T11
|
NA
|
|
E2A-PBX1-C8
|
T13B
|
CCR
|
|
E2A-PBX1-#8
|
T11
|
NA
|
|
E2A-PBX1-C9
|
T13B
|
CCR
|
|
E2A-PBX1-#9
|
T12
|
NA
|
|
E2A-PBX1-C10
|
T13B
|
CCR
|
|
E2A-PBX1-#10
|
T12
|
NA
|
|
E2A-PBX1-C11
|
T13B
|
CCR
|
|
E2A-PBX1-#11
|
T14
|
NA
|
|
E2A-PBX1-C12
|
T13B
|
CCR
|
|
E2A-PBX1-#12
|
T15
|
NA
|
|
E2A-PBX1-R1
|
T13B
|
Heme Relapse
|
|
E2A-PBX1-#13
|
T15
|
NA
|
|
E2A-PBX1-2M#1
|
T13B
|
2nd AML
|
|
|
|
|
| |
|
|
|
|
|
|
Hyperdip>50
subgroup (n=64)
|
|
Hyperdip>50-C1
|
T13A
|
CCR
|
|
Hyperdip>50-C33
|
T13B
|
CCR
|
|
Hyperdip>50-C2
|
T13A
|
CCR
|
|
Hyperdip>50-C34
|
T13B
|
CCR
|
|
Hyperdip>50-C3
|
T13A
|
CCR
|
|
Hyperdip>50-C35
|
T13B
|
CCR
|
|
Hyperdip>50-C4
|
T13A
|
CCR
|
|
Hyperdip>50-C36
|
T13B
|
CCR
|
|
Hyperdip>50-C5
|
T13A
|
CCR
|
|
Hyperdip>50-C37
|
T13B
|
CCR
|
|
Hyperdip>50-C6
|
T13A
|
CCR
|
|
Hyperdip>50-C38
|
T13B
|
CCR
|
|
Hyperdip>50-C7
|
T13A
|
CCR
|
|
Hyperdip>50-C39
|
T13B
|
CCR
|
|
Hyperdip>50-C8
|
T13A
|
CCR
|
|
Hyperdip>50-C40
|
T13B
|
CCR
|
|
Hyperdip>50-C9
|
T13A
|
CCR
|
|
Hyperdip>50-C41
|
T13B
|
CCR
|
|
Hyperdip>50-C10
|
T13A
|
CCR
|
|
Hyperdip>50-C42
|
T13B
|
CCR
|
|
Hyperdip>50-C11
|
T13A
|
CCR
|
|
Hyperdip>50-C43
|
T13B
|
CCR
|
|
Hyperdip>50-C12
|
T13A
|
CCR
|
|
Hyperdip>50-R1
|
T13A
|
Heme Relapse
|
|
Hyperdip>50-C13
|
T13A
|
CCR
|
|
Hyperdip>50-R2
|
T13A
|
Heme Relapse
|
|
Hyperdip>50-C14
|
T13A
|
CCR
|
|
Hyperdip>50-R3
|
T13A
|
Heme Relapse
|
|
Hyperdip>50-C15
|
T13B
|
CCR
|
|
Hyperdip>50-R4
|
T13B
|
Heme Relapse
|
|
Hyperdip>50-C16
|
T13B
|
CCR
|
|
Hyperdip>50-R5
|
T13B
|
Heme Relapse
|
|
Hyperdip>50-C17
|
T13B
|
CCR
|
|
Hyperdip>50-2M#1
|
T13A
|
2nd AML
|
|
Hyperdip>50-C18
|
T13B
|
CCR
|
|
Hyperdip>50-2M#2
|
T13B
|
2nd AML
|
|
Hyperdip>50-C19
|
T13B
|
CCR
|
|
Hyperdip>50-#1
|
T13A
|
Censored
|
|
Hyperdip>50-C20
|
T13B
|
CCR
|
|
Hyperdip>50-#2
|
T13B
|
Censored
|
|
Hyperdip>50-C21
|
T13B
|
CCR
|
|
Hyperdip>50-#3
|
Others
|
NA
|
|
Hyperdip>50-C22
|
T13B
|
CCR
|
|
Hyperdip>50-#4
|
Others
|
NA
|
|
Hyperdip>50-C23
|
T13B
|
CCR
|
|
Hyperdip>50-#5
|
T12
|
NA
|
|
Hyperdip>50-C24
|
T13B
|
CCR
|
|
Hyperdip>50-#6
|
T15
|
NA
|
|
Hyperdip>50-C25
|
T13B
|
CCR
|
|
Hyperdip>50-#7
|
T15
|
NA
|
|
Hyperdip>50-C26
|
T13B
|
CCR
|
|
Hyperdip>50-#8
|
T15
|
NA
|
|
Hyperdip>50-C27-N
|
T13B
|
CCR
|
|
Hyperdip>50-#9
|
T15
|
NA
|
|
Hyperdip>50-C28
|
T13B
|
CCR
|
|
Hyperdip>50-#10
|
T15
|
NA
|
|
Hyperdip>50-C29
|
T13B
|
CCR
|
|
Hyperdip>50-#11
|
T15
|
NA
|
|
Hyperdip>50-C30
|
T13B
|
CCR
|
|
Hyperdip>50-#12
|
T15
|
NA
|
|
Hyperdip>50-C31
|
T13B
|
CCR
|
|
Hyperdip>50-#13
|
T15
|
NA
|
|
Hyperdip>50-C32
|
T13B
|
CCR
|
|
Hyperdip>50-#14
|
T15
|
NA
|
| |
|
|
|
|
|
|
|
Hyperdip47-50
subgroup (n=23)
|
|
Hyperdip47-50-C1
|
T13A
|
CCR
|
|
Hyperdip47-50-C13
|
T13B
|
CCR
|
|
Hyperdip47-50-C2
|
T13A
|
CCR
|
|
Hyperdip47-50-C14-N
|
T13B
|
CCR
|
|
Hyperdip47-50-C3-N
|
T13A
|
CCR
|
|
Hyperdip47-50-C15
|
T13B
|
CCR
|
|
Hyperdip47-50-C4
|
T13A
|
CCR
|
|
Hyperdip47-50-C16
|
T13B
|
CCR
|
|
Hyperdip47-50-C5
|
T13A
|
CCR
|
|
Hyperdip47-50-C17
|
T13B
|
CCR
|
|
Hyperdip47-50-C6
|
T13B
|
CCR
|
|
Hyperdip47-50-C18
|
T13B
|
CCR
|
|
Hyperdip47-50-C7
|
T13B
|
CCR
|
|
Hyperdip47-50-C19
|
T13B
|
CCR
|
|
Hyperdip47-50-C8
|
T13B
|
CCR
|
|
Hyperdip47-50-2M#1
|
T13A
|
2nd AML
|
|
Hyperdip47-50-C9
|
T13B
|
CCR
|
|
Hyperdip47-50-#1
|
T15
|
NA
|
|
Hyperdip47-50-C10
|
T13B
|
CCR
|
|
Hyperdip47-50-#2
|
T15
|
NA
|
|
Hyperdip47-50-C11
|
T13B
|
CCR
|
|
Hyperdip47-50-#3
|
T15
|
NA
|
|
Hyperdip47-50-C12
|
T13B
|
CCR
|
|
|
|
|
| |
|
|
|
|
|
|
Hypodip
subgroup (n=9)
|
|
Hypodip-C1
|
T13A
|
CCR
|
|
Hypodip-C6
|
T13B
|
CCR
|
|
Hypodip-C2
|
T13A
|
CCR
|
|
Hypodip-2M#1
|
T13A
|
2nd AML
|
|
Hypodip-C3
|
T13B
|
CCR
|
|
Hypodip-#1
|
T15
|
NA
|
|
Hypodip-C4
|
T13B
|
CCR
|
|
Hypodip-#2
|
T15
|
NA
|
|
Hypodip-C5
|
T13B
|
CCR
|
|
|
|
|
| |
|
|
|
|
|
|
MLL subgroup
(n=20)
|
|
MLL-C1
|
T13A
|
CCR
|
|
MLL-2M#1
|
T13A
|
2nd AML
|
|
MLL-C2
|
T13B
|
CCR
|
|
MLL-2M#2
|
T13A
|
2nd AML
|
|
MLL-C3
|
T13B
|
CCR
|
|
MLL-#1
|
T13B
|
Censored
|
|
MLL-C4
|
T13B
|
CCR
|
|
MLL-#2
|
T13B
|
Censored
|
|
MLL-C5
|
T13B
|
CCR
|
|
MLL-#3
|
Others
|
NA
|
|
MLL-C6
|
T13B
|
CCR
|
|
MLL-#4
|
Others
|
NA
|
|
MLL-R1
|
T13A
|
Heme Relapse
|
|
MLL-#5
|
Others
|
NA
|
|
MLL-R2
|
T13A
|
Heme Relapse
|
|
MLL-#6
|
T12
|
NA
|
|
MLL-R3
|
T13B
|
Heme Relapse
|
|
MLL-#7
|
T14
|
NA
|
|
MLL-R4
|
T13B
|
Heme Relapse
|
|
MLL-#8
|
T14
|
NA
|
| |
|
|
|
|
|
|
Normal
subgroup (n=18)
|
|
Normal-C1-N
|
T13A
|
CCR
|
|
Normal-C10
|
T13B
|
CCR
|
|
Normal-C2-N
|
T13A
|
CCR
|
|
Normal-C11-N
|
T13B
|
CCR
|
|
Normal-C3-N
|
T13A
|
CCR
|
|
Normal-C12
|
T13B
|
CCR
|
|
Normal-C4-N
|
T13B
|
CCR
|
|
Normal-R1
|
T13A
|
Heme Relapse
|
|
Normal-C5
|
T13B
|
CCR
|
|
Normal-R2-N
|
T13B
|
Heme Relapse
|
|
Normal-C6
|
T13B
|
CCR
|
|
Normal-R3
|
T13B
|
Heme Relapse
|
|
Normal-C7-N
|
T13B
|
CCR
|
|
Normal-#1
|
T13A
|
Censored
|
|
Normal-C8
|
T13B
|
CCR
|
|
Normal-#2
|
T13B
|
Censored
|
|
Normal-C9
|
T13B
|
CCR
|
|
Normal-#3
|
T13B
|
Censored
|
| |
|
|
|
|
|
|
Pseudodip
subgroup (n=29)
|
|
Pseudodip-C1
|
T13A
|
CCR
|
|
Pseudodip-C16-N
|
T13B
|
CCR
|
|
Pseudodip-C2-N
|
T13A
|
CCR
|
|
Pseudodip-C17
|
T13B
|
CCR
|
|
Pseudodip-C3
|
T13A
|
CCR
|
|
Pseudodip-C18
|
T13B
|
CCR
|
|
Pseudodip-C4
|
T13A
|
CCR
|
|
Pseudodip-C19
|
T13B
|
CCR
|
|
Pseudodip-C5
|
T13A
|
CCR
|
|
Pseudodip-R1-N
|
T13A
|
Heme Relapse
|
|
Pseudodip-C6
|
T13A
|
CCR
|
|
Pseudodip-#1
|
T13B
|
Other Relapse
|
|
Pseudodip-C7
|
T13A
|
CCR
|
|
Pseudodip-#2
|
T13B
|
Censored
|
|
Pseudodip-C8
|
T13A
|
CCR
|
|
Pseudodip-#3
|
Others
|
NA
|
|
Pseudodip-C9
|
T13A
|
CCR
|
|
Pseudodip-#4
|
Others
|
NA
|
|
Pseudodip-C10
|
T13B
|
CCR
|
|
Pseudodip-#5
|
T15
|
NA
|
|
Pseudodip-C11
|
T13B
|
CCR
|
|
Pseudodip-#6
|
T15
|
NA
|
|
Pseudodip-C12
|
T13B
|
CCR
|
|
Pseudodip-#7
|
T15
|
NA
|
|
Pseudodip-C13
|
T13B
|
CCR
|
|
Pseudodip-#8-N
|
T15
|
NA
|
|
Pseudodip-C14
|
T13B
|
CCR
|
|
Pseudodip-#9
|
T15
|
NA
|
|
Pseudodip-C15
|
T13B
|
CCR
|
|
|
|
|
| |
|
|
|
|
|
|
T-ALL
subgroup (n=43)
|
|
T-ALL-C1
|
T13A
|
CCR
|
|
T-ALL-C23
|
T13B
|
CCR
|
|
T-ALL-C2
|
T13A
|
CCR
|
|
T-ALL-C24
|
T13B
|
CCR
|
|
T-ALL-C3
|
T13A
|
CCR
|
|
T-ALL-C25
|
T13B
|
CCR
|
|
T-ALL- | |
