Page 140 - 2019_01-Haematologica-web

K. Ohki et al.
Microarray and data analyses
The gene expression signature for MEF2D fusion-positive B- ALL was investigated by DNA microarray-based expression pro- filing using Human Genome U133 Plus 2.0 Arrays (Affymetrix, Santa Clara, CA, USA). Data were normalized and filtered as described previously.11 Further details are provided in Online Supplementary Methods.
Table 1. Characteristics of MEF2D fusion-positive cases.
Statistical analysis
Mutual univariate analyses of characteristics were conducted using Fisher’s exact test or the c2 test for qualitative variables. Overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method and compared by the log-rank test. Analyses were performed using Prism software, version 6.0 (GraphPad Software, Inc., La Jolla, CA, USA).
Initial Day8 Relapse Relapse Salvage FUP Current Samples Fusion risk blasts (site) date therapy (years) status obtained points
(NCI) (/L) (years) after at relapse
Case Fusion Identified Age Sex Diagnosis Initial partner (years) WBC (/ L)
Karyotype
1 BCL9
2 BCL9 3 BCL9 4 BCL9 5 BCL9 6 BCL9 7 BCL9
8 BCL9 9 BCL9
10 BCL9
11 HNRNPUL1
12 HNRNPUL1 RT-PCR 8 F
46,XX,-X,add(3)(q27), IR 0 No - - 10.9+ 1st Newly Ex4-4bp*
RT-PCR 8 F
B-ALL
3,400
RT-PCR WTS/RT-PCR WTS/RT-PCR WTS RT-PCR RT-PCR
9 F 15 F 10 M
7 M
9 F
9 F
46,XX[20] 46,XX[20]
IR 40
HR 0 Yes(CNS) 1.1
HR 63 No - - 9.1+ 1st CR
B-ALL
B-ALL
B-ALL 124,100 NA
add(9)(q13),add(9)(q13), add(10)(q22),-12,del(12)(q13), del(13)(q12q14) -20,+22,+2mar[ cp3]/46,XX[2]
CR
diagnosed 1 ins-Ex9
Newly Ex6-Ex10 diagnosed
Newly Ex9-Ex9, diagnosed Ex5-Ex9 Newly Ex6-Ex10
diagnosed
Newly Ex5-Ex9
diagnosed
Newly Ex6-Ex10
diagnosed
Newly Ex5-Ex10,
diagnosed, Ex6-Ex10
1st relapse
29,400 63,200
Yes (BM) 1.0
Chemo
SCT 2.0 Dead
1.2 Dead
B-ALL
B-ALL
B-ALL
B-ALL
B-ALL
B-LBL
B-ALL
B-ALL
B-ALL
77,300
41,400
46,200
NA
5,400
NA
5,300
8,200
27,300
45,XY,t(1;2)(q21;p13),-9, i(9)(q10),add(16)(q13)[20]
NA IR30
NA IR18
Yes (BM) 2.0
Yes (CNS) 0.8
Yes (BM) 1.6
SCT 2.6 Dead
Chemo 1.9 Dead
SCT 4.2 Dead
IR 240
WTS/RT-PCR
10 F
NA
NA
46,XX[4]
NA
NA
46,XX[18]
47,XX,t(3;9)
HR NA
NA
NA NA NA NA Newly Ex5-Ex9,
RT-PCR 3 M
diagnosed Ex6-Ex9*2 SR 25 No - - 13.1+ 1stCR Newly Ex5-Ex9
diagnosed
WTS/RT-PCR 7 F
Stage IVNA No - - 5.4+1stCR Newly Ex6-Ex10 diagnosed
WTS/RT-PCR 9 M
IR 0 No - - 8.6+ 1st CR Newly Ex9-Ex12 diagnosed
IR 54 No - - 9.9+ 1st CR Newly Ex9-Ex12 diagnosed
13 HNRNPUL1 WTS/RT-PCR
14 HNRNPUL1 WTS/RT-PCR
15 HNRNPUL1 WTS/RT-PCR
16 HNRNPUL1 RT-PCR
17 HNRNPH1 WTS/RT-PCR
5 F
15 M
10 F
14 M
7 F
SR 736 Yes (BM) 1.3 SCT 1.9 Dead Newly Ex9-Ex12 diagnosed
B-ALL 6,200 fail
B-ALL 21,900
B-ALL 10,800
B-ALL 76,100
IR 0 No - - 4.5+ 1st CR Newly Ex9-Ex12 diagnosed
HR 750 Yes (BM) 1.9 Chemo, SCT 2.4 Dead Newly Ex9-Ex12 diagnosed
46,XY,?ins(9)(q13p22p24)[20] HR 1,134 No - - 7.5+ 1st CR Newly Ex9-Ex12 diagnosed
46,XX,t(1;5)(q21;q35) IR NA Yes(BM) 1.2 Chemo 1.8 Dead Newly Ex4-Ex5
[8]/47,idem,+8[8]/46,XX[2] diagnosedEx7-21bp*4
ins-Ex5
RT-PCR: Reverse Transcription Polymerase Chain Reaction; WTS: Whole Transcriptome Sequencing; WBC: white blood cells; CNS: central nervous system; FUP: follow up; B-ALL: precursor B- cell acute lymphoblastic leukemia; B-LBL: precursor B-cell lymphoblastic lymphoma; NCI: National Cancer Institute; SR: standard risk; IR: intermediate risk; HR: high risk; Ex: exon; BM: bone marrow; CR: complete remission; NA: data not available; SCT: stem-cell transplantation; Chemo: chemotherapy. *1: (TGTC). *2: Ex6-Ex9 fusion was detected only by WTS. *3: The PAX5-FOXP1 translocation was not detected by whole transcriptome sequencing. *4: (CCCGACCGACTTGTGTTCCGC).
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haematologica | 2019; 104(1)