TO THE EDITOR:

Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subtype of B-precursor ALL (B-ALL) characterized by a gene-expression profile similar to Ph+ ALL but lacking the specific BCR-ABL1 fusion gene.1,2  Patients with Ph-like ALL are at higher risk of induction failure or high postinduction minimal residual disease (MRD) levels.3-5  This poor early response translates into inferior outcome in event-free survival (EFS) and overall survival (OS) as compared with other B-ALL patients. Ph-like ALL was recognized as a provisional entity by the 2016 World Health Organization (WHO) classification but strict and unequivocal diagnosis criteria have not yet been established.6  Ph-like ALL harbors diverse oncogenic lesions that all lead to the aberrant activation of cytokine receptors or signaling factors, the most frequent being rearrangements of CRLF2, fusions and mutations of JAK kinases, and fusions involving ABL-class kinases (ABL1, ABL2, CSF1R, or PDGFRB).7  As anticipated, Ph-like cells harboring ABL-class rearrangements have shown sensitivity to tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib in vitro or in patient-derived xenograft.8-10  In addition, we and others have reported single experiences of clinical benefit of TKI treatment in early resistant patients.11,12 

In an attempt to enable targeted therapy in B-ALL patients with poor response to chemotherapy, we developed an integrative diagnosis strategy to identify Ph-like alterations in newly diagnosed or relapsing patients in a timely manner. We report on 24 patients with B-ALL harboring ABL-class fusions, initially enrolled in or treated according to pediatric (French Acute Lymphoblastic Leukaemia Study Group [FRALLE]/French Protocol for the Treatment of Acute Lymphoblastic Leukemia in Children and Adolescents [CAALL]/European Organisation for Research and Treatment of Cancer [EORTC]) (NCT02716233; NCT01185886) or adult (French-Swiss-Belgian Group for Research on Adult Acute Lymphoblastic Leukemia [GRAALL]/European Working Group on Adult ALL [EWALL]) (NCT00327678; NCT02617004) trials, who could be treated with a combination of TKI and chemotherapy, either during frontline treatment (N = 19) or at relapse (N = 5). Cytogenetic analyses were performed locally. Molecular analyses were performed centrally using in-house, multiplexed targeted methods13  for detection of fusion transcripts, and in a second step, RNA sequencing for unresolved cases. The current algorithm of our screening strategy is shown in supplemental Figure 1 (available on the Blood Web site).

Of the 24 patients reported here, 12 had fusions involving ABL1, including NUP214-ABL1 (n = 6), ETV6-ABL1 (n = 3), and other partners in single cases (RCSD1, RANBP2, and LSM14A) (Figure 1A). Nine cases had a PDGFRB rearrangement, including EBF1-PDGFRB (n = 6) and other partners in single cases (NUMA1, ETV6, and ATF7IP). ZC3HAV1-ABL2 and MEF2D-CSF1R fusions were identified in single cases, and a patient with a ZMYM2-FGFR1 fusion (not strictly ABL class) was also included in the present cohort.

Figure 1.

Patient characteristics and outcome. (A) ABL-class fusion gene in the whole cohort (N = 24). On the circos plot, the names of ABL-class genes are in blue; partner genes are in red. (B) MRD response in patients treated frontline at different time points (N = 19, 1 patient not evaluated after TKI exposure). EFS (C) and OS (D) from diagnosis in patients exposed frontline to TKI (N = 19).

Figure 1.

Patient characteristics and outcome. (A) ABL-class fusion gene in the whole cohort (N = 24). On the circos plot, the names of ABL-class genes are in blue; partner genes are in red. (B) MRD response in patients treated frontline at different time points (N = 19, 1 patient not evaluated after TKI exposure). EFS (C) and OS (D) from diagnosis in patients exposed frontline to TKI (N = 19).

Close modal

The resulting cohort (Table 1) included 16 male and 8 female patients; the median age at diagnosis was 24 years (range, 5-72 years). Two patients (#1 and #24) were previously reported.11,14  As expected, patients had baseline characteristics and early response to treatment associated with a poor prognosis. The median white blood cell count was 30 × 109/L (range, 4 × 109/L to 570 × 109/L). Intragenic IKZF1 deletions were detected in 11 of 24 patients (46%). A poor response to prednisone prephase (≥1 × 109/L blasts in peripheral blood at day 8) was observed in 14 of 22 evaluable patients (64%). After induction therapy, only 16 of 24 patients (67%) reached complete remission (CR), all with detectable MRD, including 7 with MRD ≥10−2 (Table 1; Figure 1B).

Table 1.

Individual patient characteristics and outcome

PatientsFusion geneSexAge, yWBC, ×109/LIKZF1Front-line trialPrednisone response, day 8MRD response to induction*Time to TKI initiation, dTKI (dose, mg daily)Treatment combined with TKIFirst MRD post-TKI (d)Best MRD in CCR (d)HSCT§Survival (mo)
In first line                
 1 EBF1-PDGFRB 16 167 del FRALLE-2000B Poor 2 × 10−1 55 Imatinib (400) Chemo 5 × 10−3 (21) Neg (50) Alive in CR1 (62) 
 2 EBF1-PDGFRB 11 154 wt FRALLE-2000B Poor 2 × 10−2 44 Imatinib (300) Chemo Neg (44) Neg (44) Alive in CR1 (50) 
 3 EBF1-PDGFRB 23 wt FRALLE-2000A Poor No CR (35%) 39 Imatinib (NA) Chemo >10−2 (18) Neg (45) Alive in CR1 (50) 
 4 EBF1-PDGFRB 15 31 wt EORTC 58081-AR1 Good 5 × 10−3 137 Imatinib (500) Chemo Neg (109) Neg (109) Alive in CR1 (43) 
 5 EBF1-PDGFRB 17 wt CAALL-01 Good No CR (60%) 38 Imatinib (550) Chemo 4 × 10−4 (48) +<10−4 (62) Alive in CR1 (23) 
 6 EBF1-PDGFRB 36 45 wt GRAALL-2014 Poor 8 × 10−3 44 Imatinib (400) Chemo +<10−4 (35) Neg (78) Alive in CR1 (23) 
 7 NUMA1-PDGFRB 61 wt VCR-DEX-Ritux Good 1 × 10−3 39 Dasatinib (100) Chemo Neg (67) Neg (67) Alive in CR2 (36) 
 8 ETV6-PDGFRB 72 16 Wt EWALL-BB Good 1 × 10−2 38 Imatinib (600) Chemo 2 × 10−3 (91) 1 × 10−4 (252) Alive in CR1 (29) 
         330 Dasatinib (NA) Chemo Neg (120) Neg (120)   
 9 ATF7IP-PDGFRB 54 13 wt GRAALL-2014 Poor 1 × 10−4 15 Dasatinib (100) Chemo 1 × 10−4 (15) Neg (77) Death in CR2 (16) 
 10 NUP214-ABL1 16 30 del EORTC 58081- Poor No CR (34%) 81 Imatinib (550) Chemo No CR (23) No CR (23) Alive in CR1 (45) 
      AR1   104 Dasatinib (140) Chemo >10−2 (71) 1 × 10−2 (114)   
 11 NUP214-ABL1 17 114 del FRALLE-2000B Good 2 × 10−1 89 Imatinib (500) Chemo, Blin 8 × 10−2 (26) Neg (54) Alive in CR1 (43) 
         98 Dasatinib (140) (114)     
 12 NUP214-ABL1 24 11 del FRALLE-2000B Poor 2 × 10−3 49 Imatinib (400) Chemo Neg (65) Neg (65) Alive in REL1 (29) 
 13 NUP214-ABL1 31 70 del GRAALL-2014 Poor No CR (12%) 61 Dasatinib (140) Chemo NA NA Death in REL1 (9) 
 14 NUP214-ABL1 18 18 wt GRAALL-2014 NA No CR (9%) 70 Dasatinib (100) Chemo 8 × 10−2 (14) Neg (125) Alive in CR1 (11) 
 15 RCSD1-ABL1 26 29 wt GRAALL-2014 Good 6 × 10−3 69 Dasatinib (NA) Chemo 2 × 10−3 (85) 5 × 10−4 (125) Alive in CR1 (27) 
 16 LSM14A-ABL1 36 390 del VCR-DEX-Ritux Poor No CR (7%) 49 Dasatinib (NA) Chemo No CR (15) NA Death, REF (2) 
 17 ZC3HAV1-ABL2 27 30 del GRAALL-2014 NA 9 × 10−4 58 Imatinib (600) Chemo 2 × 10−4 (44) Neg (175) Alive in CR1 (8) 
 18 MEF2D-CSF1R 34 89 wt GRAALL-2014 Poor 1 × 10−2 20 Imatinib (NA) Chemo 1 × 10−4 (96) Neg (147) Death in REL1 (13) 
 19 ZMYM2-FGFR1 23 53 wt GRAALL-2005 Poor No CR (55%) 67 Ponatinib (30) Chemo 2 × 10−2 (39) 2 × 10−3 (175) Death in REL3 (37) 
In relapse                
 20 ETV6-ABL1 12 NA del FRALLE-2000B Good +<10−4 REL1 Dasatinib (100) Chemo Neg (25) Neg (25) Alive in CR2 (124) 
 21 ETV6-ABL1 14 570 del FRALLE-2000B Poor 2 × 10−2 REL1 Imatinib (NA) Chemo 1 × 10−3 (21) +<10−4 (49) Alive in CR2 (59) 
 22 RANBP2-ABL1 20 del GRAALL-2005R Good <10−4 REL2, REF Dasatinib (140) Chemo 7 × 10−2 (60) 8 × 10−3 (87) Death in REL3 (29) 
 23 ETV6-ABL1 61 10 wt EWALL-BB Poor No CR (75%) REL1 Imatinib (400) Chemo 5 × 10−3 (34) Neg (245) Death in REL2 (28) 
 24 NUP214-ABL1 15 237 del EORTC 58081-VHR Poor >10−2 REL3 Dasatinib (140) Chemo, DLI 3 × 10−2 (27) NA Death in REL5 (60) 
PatientsFusion geneSexAge, yWBC, ×109/LIKZF1Front-line trialPrednisone response, day 8MRD response to induction*Time to TKI initiation, dTKI (dose, mg daily)Treatment combined with TKIFirst MRD post-TKI (d)Best MRD in CCR (d)HSCT§Survival (mo)
In first line                
 1 EBF1-PDGFRB 16 167 del FRALLE-2000B Poor 2 × 10−1 55 Imatinib (400) Chemo 5 × 10−3 (21) Neg (50) Alive in CR1 (62) 
 2 EBF1-PDGFRB 11 154 wt FRALLE-2000B Poor 2 × 10−2 44 Imatinib (300) Chemo Neg (44) Neg (44) Alive in CR1 (50) 
 3 EBF1-PDGFRB 23 wt FRALLE-2000A Poor No CR (35%) 39 Imatinib (NA) Chemo >10−2 (18) Neg (45) Alive in CR1 (50) 
 4 EBF1-PDGFRB 15 31 wt EORTC 58081-AR1 Good 5 × 10−3 137 Imatinib (500) Chemo Neg (109) Neg (109) Alive in CR1 (43) 
 5 EBF1-PDGFRB 17 wt CAALL-01 Good No CR (60%) 38 Imatinib (550) Chemo 4 × 10−4 (48) +<10−4 (62) Alive in CR1 (23) 
 6 EBF1-PDGFRB 36 45 wt GRAALL-2014 Poor 8 × 10−3 44 Imatinib (400) Chemo +<10−4 (35) Neg (78) Alive in CR1 (23) 
 7 NUMA1-PDGFRB 61 wt VCR-DEX-Ritux Good 1 × 10−3 39 Dasatinib (100) Chemo Neg (67) Neg (67) Alive in CR2 (36) 
 8 ETV6-PDGFRB 72 16 Wt EWALL-BB Good 1 × 10−2 38 Imatinib (600) Chemo 2 × 10−3 (91) 1 × 10−4 (252) Alive in CR1 (29) 
         330 Dasatinib (NA) Chemo Neg (120) Neg (120)   
 9 ATF7IP-PDGFRB 54 13 wt GRAALL-2014 Poor 1 × 10−4 15 Dasatinib (100) Chemo 1 × 10−4 (15) Neg (77) Death in CR2 (16) 
 10 NUP214-ABL1 16 30 del EORTC 58081- Poor No CR (34%) 81 Imatinib (550) Chemo No CR (23) No CR (23) Alive in CR1 (45) 
      AR1   104 Dasatinib (140) Chemo >10−2 (71) 1 × 10−2 (114)   
 11 NUP214-ABL1 17 114 del FRALLE-2000B Good 2 × 10−1 89 Imatinib (500) Chemo, Blin 8 × 10−2 (26) Neg (54) Alive in CR1 (43) 
         98 Dasatinib (140) (114)     
 12 NUP214-ABL1 24 11 del FRALLE-2000B Poor 2 × 10−3 49 Imatinib (400) Chemo Neg (65) Neg (65) Alive in REL1 (29) 
 13 NUP214-ABL1 31 70 del GRAALL-2014 Poor No CR (12%) 61 Dasatinib (140) Chemo NA NA Death in REL1 (9) 
 14 NUP214-ABL1 18 18 wt GRAALL-2014 NA No CR (9%) 70 Dasatinib (100) Chemo 8 × 10−2 (14) Neg (125) Alive in CR1 (11) 
 15 RCSD1-ABL1 26 29 wt GRAALL-2014 Good 6 × 10−3 69 Dasatinib (NA) Chemo 2 × 10−3 (85) 5 × 10−4 (125) Alive in CR1 (27) 
 16 LSM14A-ABL1 36 390 del VCR-DEX-Ritux Poor No CR (7%) 49 Dasatinib (NA) Chemo No CR (15) NA Death, REF (2) 
 17 ZC3HAV1-ABL2 27 30 del GRAALL-2014 NA 9 × 10−4 58 Imatinib (600) Chemo 2 × 10−4 (44) Neg (175) Alive in CR1 (8) 
 18 MEF2D-CSF1R 34 89 wt GRAALL-2014 Poor 1 × 10−2 20 Imatinib (NA) Chemo 1 × 10−4 (96) Neg (147) Death in REL1 (13) 
 19 ZMYM2-FGFR1 23 53 wt GRAALL-2005 Poor No CR (55%) 67 Ponatinib (30) Chemo 2 × 10−2 (39) 2 × 10−3 (175) Death in REL3 (37) 
In relapse                
 20 ETV6-ABL1 12 NA del FRALLE-2000B Good +<10−4 REL1 Dasatinib (100) Chemo Neg (25) Neg (25) Alive in CR2 (124) 
 21 ETV6-ABL1 14 570 del FRALLE-2000B Poor 2 × 10−2 REL1 Imatinib (NA) Chemo 1 × 10−3 (21) +<10−4 (49) Alive in CR2 (59) 
 22 RANBP2-ABL1 20 del GRAALL-2005R Good <10−4 REL2, REF Dasatinib (140) Chemo 7 × 10−2 (60) 8 × 10−3 (87) Death in REL3 (29) 
 23 ETV6-ABL1 61 10 wt EWALL-BB Poor No CR (75%) REL1 Imatinib (400) Chemo 5 × 10−3 (34) Neg (245) Death in REL2 (28) 
 24 NUP214-ABL1 15 237 del EORTC 58081-VHR Poor >10−2 REL3 Dasatinib (140) Chemo, DLI 3 × 10−2 (27) NA Death in REL5 (60) 

Blin, blinatumomab; CAALL, French Protocol for the Treatment of Acute Lymphoblastic Leukemia in Children and Adolescents; CCR, continuous complete remission; Chemo, polychemotherapy; CR, complete remission; CR1, complete remission 1; CR2, complete remission 2; del, intragenic deletion; DLI, donor lymphocyte infusion; EORTC, European Organisation for Research and Treatment of Cancer; EWALL, European Working Group on Adult ALL; F, female; FRALLE, French Acute Lymphoblastic Leukaemia Study Group; GRAALL, French-Swiss-Belgian Group for Research on Adult Acute Lymphoblastic Leukemia; M, male; NA, not available; Neg, negative; REF, refractory; REL1, relapse 1; REL2, relapse 2; REL3, relapse 3; REL5, relapse 5; VCR-DEX-Ritux, vincristine-dexamethasone-rituximab; VHR, very high risk; WBC, white blood cell count; wt, wild type.

*

MRD in case of morphological CR, or the percentage of blasts in refractory patients.

From diagnosis, or disease status for patients in relapse.

From TKI initiation.

§

HSCT in CCR after TKI initiation.

In 19 patients, the ABL-class fusion was identified at initial diagnosis workup and TKI was introduced during frontline treatment, most frequently within the first month of consolidation or salvage (median 49 days from diagnosis). In 5 patients, ABL-class fusions were diagnosed at relapse and TKI was introduced in association with salvage therapy. Remarkably, 2 of these patients had postinduction MRD below 10−4 during frontline treatment. In this study, the physician chose the TKI, TKI dosage, and combination. Fourteen patients were exposed to imatinib, 9 to dasatinib, and 1 to ponatinib. Three patients were switched from imatinib to dasatinib during frontline treatment (Table 1).

Among the 19 patients treated with TKI frontline, 6 of 7 primary refractory patients subsequently achieved CR, 1 after a switch to dasatinib (#10). One patient died early of sepsis in a context of uncontrolled disease (#16). One patient was lost of follow-up after salvage until she relapsed (#13). In 14 of 18 patients (78%), an MRD level below 10−4 was achieved within a median time of 2.5 months (range, 1.4-14.8 months) after TKI initiation (Figure 1B). Allogeneic hematopoietic stem cell transplant (HSCT) was performed in 9 patients, 3 with a sibling donor, 4 with a matched unrelated donor (MUD), and 2 with a haploidentical donor (Haplo). All patients were in CR before HSCT and 6 of 9 (67%) had undetectable MRD. One patient was additionally exposed to blinatumomab in combination to dasatinib in bridge to HSCT. After a median follow-up of 36 months (range, 8-73 months), 12 patients were alive in first CR. Six patients relapsed; 3 patients received an alternative TKI, including 1 in association to inotuzumab. The median remission duration and OS were not reached. At 3 years, EFS was 55% (95% confidence interval, 27-76) and OS was 77% (95% confidence interval, 50-91) (Figure 1C-D).

The 5 patients who were treated with TKI at relapse achieved CR, including 2 patients who had refractory disease to several lines of treatment (#22 and #24). An MRD level below 10−4 was achieved in 3 patients, of whom 2 could proceed to HSCT (1 haploidentical donor, 1 matched unrelated donor) and remained alive in remission. The 3 other patients further relapsed and died of progressive disease after exposure to second-line TKIs (dasatinib, n = 2; ponatinib, n = 1).

Although anecdotal reports of clinical efficacy of TKIs in patients with ABL-class mutant Ph-like ALL have been described,8,11,12,15-17  more systematic TKI introduction has been severely hampered by the diagnostic challenge of detecting previously unknown 5′ fusion partners in a timely manner. We report here a significant cohort of patients for whom identification of ABL-class fusions led to early introduction of TKI therapy. Previous adult studies have reported the poor outcome of Ph-like ALL in adults with 5-year OS ranging from 22% to 27%.3-5  The 3-year OS of 77% we observed in the patients treated frontline compares favorably with these retrospective observations. Beyond the use of historical cohort, this comparison has, however, some limitations. Indeed, the historical series included all Ph-like ALL cases characterized by gene-expression profile, and no specific subgroup analysis was performed in patients with ABL-class fusion genes. The outcome of non-CRLF2-rearranged patients was suggested to be better than CRLF2-rearranged cases, which may lead to underestimation of the outcome of ABL-class mutant Ph-like ALL treated without TKI.4  However, considering the highly resistant profile of our patients after induction, the outcome with conventional therapy was expected to be poor. Finally, the outcome of children and adolescents, a minority of patients in our cohort, has been reported to be better than in adults, which may reflect the use of more intensive chemotherapy regimen.8 

In conclusion, we report the largest cohort of patients with ABL-class kinase rearrangement exposed to TKI frontline or at relapse, and show promising MRD response and outcome, reminiscent of those observed in early trials of imatinib combined with chemotherapy in Ph+ ALL.18  Prospective screening strategies are feasible and should be generalized to identify these high-risk patients and to propose early TKI-based intervention. In future studies, several questions remain to be addressed, including the choice of TKI according to the fusion transcript, whether these patients should receive recently approved blinatumomab,19  and finally the benefit of HSCT in patients who achieve good MRD response upon targeted therapy.

The online version of this article contains a data supplement.

This work was supported by a grant from Le Fonds de Dotation Contre la Leucémie (JNCL 2014-01).

Contribution: I.T. collected and analyzed data and wrote the manuscript; I.B. performed experiments and analyzed data; N.S., T.B., A.T.-S., J.T., S.M., E.D., C.H., C.D., P.C., P.R., A.B., J.L.-P., and N.B. treated patients and provided clinical data; W.C., P.B., N.D., and H.C. provided molecular and cytogenetic data; M.B. analyzed data and wrote the manuscript; H.D. and J.S. contributed to the study design and wrote the manuscript; N.B. and E.C. designed research, collected and analyzed data, and wrote the manuscript; and all authors reviewed the manuscript.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Nicolas Boissel, Hematology Department, Saint-Louis Hospital, 1 Ave Claude Vellefaux, 75010 Paris, France; e-mail: nicolas.boissel@aphp.fr.

1.
Den Boer
ML
,
van Slegtenhorst
M
,
De Menezes
RX
, et al
.
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study
.
Lancet Oncol
.
2009
;
10
(
2
):
125
-
134
.
2.
Harvey
RC
,
Mullighan
CG
,
Wang
X
, et al
.
Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome
.
Blood
.
2010
;
116
(
23
):
4874
-
4884
.
3.
Roberts
KG
,
Gu
Z
,
Payne-Turner
D
, et al
.
High frequency and poor outcome of Philadelphia chromosome-like acute lymphoblastic leukemia in adults
.
J Clin Oncol
.
2017
;
35
(
4
):
394
-
401
.
4.
Jain
N
,
Roberts
KG
,
Jabbour
E
, et al
.
Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults
.
Blood
.
2017
;
129
(
5
):
572
-
581
.
5.
Herold
T
,
Schneider
S
,
Metzeler
KH
, et al
.
Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis
.
Haematologica
.
2017
;
102
(
1
):
130
-
138
.
6.
Arber
DA
,
Orazi
A
,
Hasserjian
R
, et al
.
The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia
.
Blood
.
2016
;
127
(
20
):
2391
-
2405
.
7.
Pui
CH
,
Roberts
KG
,
Yang
JJ
,
Mullighan
CG
.
Philadelphia chromosome-like acute lymphoblastic leukemia
.
Clin Lymphoma Myeloma Leuk
.
2017
;
17
(
8
):
464
-
470
.
8.
Roberts
KG
,
Li
Y
,
Payne-Turner
D
, et al
.
Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia
.
N Engl J Med
.
2014
;
371
(
11
):
1005
-
1015
.
9.
Tasian
SK
,
Teachey
DT
,
Li
Y
, et al
.
Potent efficacy of combined PI3K/mTOR and JAK or ABL inhibition in murine xenograft models of Ph-like acute lymphoblastic leukemia
.
Blood
.
2017
;
129
(
2
):
177
-
187
.
10.
Maude
SL
,
Tasian
SK
,
Vincent
T
, et al
.
Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia
.
Blood
.
2012
;
120
(
17
):
3510
-
3518
.
11.
Lengline
E
,
Beldjord
K
,
Dombret
H
,
Soulier
J
,
Boissel
N
,
Clappier
E
.
Successful tyrosine kinase inhibitor therapy in a refractory B-cell precursor acute lymphoblastic leukemia with EBF1-PDGFRB fusion
.
Haematologica
.
2013
;
98
(
11
):
e146
-
e148
.
12.
Weston
BW
,
Hayden
MA
,
Roberts
KG
, et al
.
Tyrosine kinase inhibitor therapy induces remission in a patient with refractory EBF1-PDGFRB-positive acute lymphoblastic leukemia
.
J Clin Oncol
.
2013
;
31
(
25
):
e413
-
e416
.
13.
Ruminy
P
,
Marchand
V
,
Buchbinder
N
, et al
.
Multiplexed targeted sequencing of recurrent fusion genes in acute leukaemia
.
Leukemia
.
2016
;
30
(
3
):
757
-
760
.
14.
Duployez
N
,
Grzych
G
,
Ducourneau
B
, et al
.
NUP214-ABL1 fusion defines a rare subtype of B-cell precursor acute lymphoblastic leukemia that could benefit from tyrosine kinase inhibitors
.
Haematologica
.
2016
;
101
(
4
):
e133
-
e134
.
15.
Collette
Y
,
Prébet
T
,
Goubard
A
, et al
.
Drug response profiling can predict response to ponatinib in a patient with t(1;9)(q24;q34)-associated B-cell acute lymphoblastic leukemia
.
Blood Cancer J
.
2015
;
5
(
3
):
e292
.
16.
Perwein
T
,
Strehl
S
,
König
M
, et al
.
Imatinib-induced long-term remission in a relapsed RCSD1-ABL1-positive acute lymphoblastic leukemia
.
Haematologica
.
2016
;
101
(
8
):
e332
-
e335
.
17.
Frech
M
,
Jehn
LB
,
Stabla
K
, et al
.
Dasatinib and allogeneic stem cell transplantation enable sustained response in an elderly patient with RCSD1-ABL1-positive acute lymphoblastic leukemia
.
Haematologica
.
2017
;
102
(
4
):
e160
-
e162
.
18.
Fielding
AK
,
Rowe
JM
,
Buck
G
, et al
.
UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia
.
Blood
.
2014
;
123
(
6
):
843
-
850
.
19.
Gökbuget
N
,
Dombret
H
,
Bonifacio
M
, et al
.
Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia
.
Blood
.
2018
;
131
(
14
):
1522
-
1531
.

Author notes

*

I.T. and I.B. contributed equally to the work.

N.B. and E.C. contributed equally to the work.

Supplemental data

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