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S. Chiaretti et al.
Table 2B. Copy number aberration (CNA) analysis, and RNA-sequencing/FISH analyses.
Record ID IKZF1 CDKN2A/2B PAX5
B-ALL_1 no-Δ no-Δ no-Δ B-ALL_3 Δ Δ Δ B-ALL_4 no-Δ no-Δ no-Δ B-ALL_7 Δ no-Δ B-ALL_16 Δ Δ B-ALL_22 Δ no-Δ no-Δ B-ALL_26 Δ no-Δ Δ B-ALL_31 Δ no-Δ Δ B-ALL_32 no-Δ no-Δ no-Δ B-ALL_34 Δ no-Δ no-Δ B-ALL_36 Δ no-Δ B-ALL_37 no-Δ no-Δ no-Δ B-ALL_41 Δ no-Δ B-ALL_44Δ Δ no-Δ Δ B-ALL_45 NA NA NA B-ALL_46 no-Δ no-Δ no-Δ B-ALL_52 no-Δ Δ Δ B-ALL_55 no-Δ no-Δ no-Δ B-ALL_61 NA NA NA B-ALL_62 NA NA NA B-ALL_64 NA NA NA B-ALL_73 Δ no-Δ no-Δ B-ALL_76 NA NA NA B-ALL_81 Δ Δ no-Δ B-ALL_92 NA NA NA B-ALL_96 Δ no-Δ Δ B-ALL_97 Δ no-Δ no-Δ B-ALL_100 no-Δ no-Δ no-Δ
IKZF1 +CDKN2A and/or PAX5
Yes
Yes Yes
Yes Yes
Yes
Yes Yes
BTG1 EBF1 CDKN2A/2B Gene
and/or RB1
DDX3X/USP9X
rearrangements (RNAseq and or FISH analysis)
no-Δ Δ no-Δ
no-Δ no-Δ Δ No
EBF1/PDGFRB
Δ no-Δ Δ No
no-Δ no-Δ Δ Δ no-Δ Δ Δ no-Δ Δ
BCR/JAK2 NUP214/ABL1
no-Δ no-Δ No
no-Δ no-Δ
no-Δ no-Δ no-Δ NA
NUP214/ABL1
P2RY8/CRLF2
IGH/CRLF2
Δ no-Δ no-Δ no-Δ no-Δ Δ
Δ no-Δ No no-Δ no-Δ Δ No
Δ no-Δ Δ
NA NA NA No
no-Δ Δ no-Δ
NA NA NA NA Δ no- Δ No NA NA NA No
The association with male sex was documented in the Total Therapy XV cohort.16 On the contrary, Roberts and colleagues28 did not find significant differences in the WBC count and sex in the standard-risk subset of childhood B-ALL patients enrolled in the COG AALL0331. In addi- tion to the WBC count and sex, it is worth underlying that in our study the population of Ph-like patients was allocat- ed to both the standard- (56%) and high-risk (44%) cate- gories: this finding has important clinical implications since the prompt identification of these cases might lead to a better therapeutic stratification that ultimately would avoid undertreating these high-risk patients. In adults, a similar distribution was reported also by Herold et al.,6 while in the pediatric setting this issue is still controver- sial. Indeed, most Ph-like cases were associated to a high risk in both the COALL and DCOG cohorts,1 while in the Total Therapy XV trial16 Ph-like cases were equally dis- tributed in the standard and high National Cancer Institute (NCI) risk groups. Of note, in the report on 139 children classified as standard-risk, Roberts and col- leagues28 showed that the Ph-like status did not affect out- come, suggesting that in children risk stratification is clin- ically more significant than the genomic features.
From a genetic standpoint, the present study further cor-
ZC3HAV1/ABL2
no-Δ no-Δ no-Δ No Δ no-Δ Δ No Δ no-Δ no-Δ No NA NA NA No NA NA NA No NA NA NA NA
BCR/JAK2
Yes Yes
Δ Δ no-Δ
NUP214/ABL1 IGH/CRLF2
Δ no-Δ no-Δ
no-Δ no-Δ no-Δ No
which MRD quantification at week 10 is pivotal for trans- plant allocation, in order to assess the prognostic impact of the Ph-like status. In particular, we aimed at understand- ing the interplay between the Ph-like status and MRD response. Furthermore, we sought to analyze the clinical and genetic features, the hematologic responses to treat- ment and the outcome of the identified Ph-like ALL patients.
The screening carried out using the BCR/ABL1-like pre- dictor7 led to the identification of 28 Ph-like cases - repre- senting 31.8% of the B-NEG cohort - with a slightly high- er incidence in adults than in young adults. This finding is in agreement with the recently reported data in other adult cohorts and resembles the epidemiologic behavior of “true Ph-positive” ALL.5,6,19 The comparison of the clinical- biological features of Ph-like and non-Ph-like cases revealed a substantial homogeneity in terms of WBC count and sex distribution, as in the GMALL and the MDACC clinical trials,6,19 and at variance from Roberts and colleagues5 who reported that adult BCR/ABL1-like patients have a higher WBC and are prevalently of male sex. In children, an association with hyperleukocyotsis has been described by Den Boer et al.1 and Reshmi et al.,27 the latter based on the COG AALL1131 high-risk cohort.
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