TO THE EDITOR:

We read with interest the recent publication by van Outersterp et al1 describing the differential sensitivity of acute lymphoblastic leukemia (ALL) ABL-class gene fusions to adenosine triphosphate (ATP)–competitive tyrosine kinase inhibitors (TKIs). The aforementioned study investigated the efficacy of imatinib, dasatinib, and bosutinib in cell lines harboring ABL1 (n = 7), ABL2 (n = 1), PDGFRB (n = 11), and CSF1R (n = 2) gene fusions and reported that lack of Src homology 3 (SH3) domain does not confer resistance to TKIs. Here, we report additional data for the efficacy of the TKIs nilotinib and ponatinib, as well as the myristate pocket–targeted allosteric inhibitor asciminib, against ABL1 (n = 5) and ABL2 (n = 3) gene fusions, collectively referred...

1.
van Outersterp
I
,
Tasian
SK
,
Reichert
CE
, et al
.
Tyrosine kinase inhibitor response of ABL-class acute lymphoblastic leukemia: the role of kinase type and SH3 domain
.
Blood
.
2024
;
143
(
21
):
2178
-
2189
.
2.
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
.
3.
Mullighan
CG
,
Su
X
,
Zhang
J
, et al
.
Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia
.
N Engl J Med
.
2009
;
360
(
5
):
470
-
480
.
4.
Hughes
TP
,
Mauro
MJ
,
Cortes
JE
, et al
.
Asciminib in chronic myeloid leukemia after ABL kinase inhibitor failure
.
N Engl J Med
.
2019
;
381
(
24
):
2315
-
2326
.
5.
Hantschel
O
.
Allosteric BCR-ABL inhibitors in Philadelphia chromosome-positive acute lymphoblastic leukemia: novel opportunities for drug combinations to overcome resistance
.
Haematologica
.
2012
;
97
(
2
):
157
-
159
.
6.
Hantschel
O
,
Nagar
B
,
Guettler
S
, et al
.
A myristoyl/phosphotyrosine switch regulates c-Abl
.
Cell
.
2003
;
112
(
6
):
845
-
857
.
7.
Nagar
B
,
Hantschel
O
,
Young
MA
, et al
.
Structural basis for the autoinhibition of c-Abl tyrosine kinase
.
Cell
.
2003
;
112
(
6
):
859
-
871
.
8.
Smith
KM
,
Yacobi
R
,
Van Etten
RA
.
Autoinhibition of Bcr-Abl through its SH3 domain
.
Mol Cell
.
2003
;
12
(
1
):
27
-
37
.
9.
Wylie
AA
,
Schoepfer
J
,
Jahnke
W
, et al
.
The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1
.
Nature
.
2017
;
543
(
7647
):
733
-
737
.
10.
Eide
CA
,
Zabriskie
MS
,
Savage Stevens
SL
, et al
.
Combining the allosteric inhibitor asciminib with ponatinib suppresses emergence of and restores efficacy against highly resistant BCR-ABL1 mutants
.
Cancer Cell
.
2019
;
36
(
4
):
431
-
443.e435
.
11.
Zhang
J
,
Adrian
FJ
,
Jahnke
W
, et al
.
Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors
.
Nature
.
2010
;
463
(
7280
):
501
-
506
.
12.
Eadie
L
,
Saunders
V
,
Branford
S
,
White
D
,
Hughes
T
.
The new allosteric inhibitor asciminib is susceptible to resistance mediated by ABCB1 and ABCG2 overexpression in vitro
.
Oncotarget
.
2018
;
9
(
17
):
13423
-
13437
.
13.
Heatley
SL
,
Asari
K
,
Schutz
CE
, et al
.
In-vitro modeling of TKI resistance in the high-risk B-cell acute lymphoblastic leukemia fusion gene RANBP2-ABL1 - implications for targeted therapy
.
Leuk Lymphoma
.
2021
;
62
(
5
):
1157
-
1166
.
14.
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
.
15.
Roberts
KG
,
Yang
Y-L
,
Payne-Turner
D
, et al
.
Oncogenic role and therapeutic targeting of ABL-class and JAK-STAT activating kinase alterations in Ph-like ALL
.
Blood Adv
.
2017
;
1
(
20
):
1657
-
1671
.
16.
Tanaka
C
,
Yin
OQ
,
Sethuraman
V
, et al
.
Clinical pharmacokinetics of the BCR-ABL tyrosine kinase inhibitor nilotinib
.
Clin Pharmacol Ther
.
2010
;
87
(
2
):
197
-
203
.
17.
Cortes
JE
,
Kantarjian
H
,
Shah
N P
, et al
.
Ponatinib in refractory Philadelphia chromosome–positive leukemias
.
N Engl J Med
.
2012
;
367
(
22
):
2075
-
2088
.
18.
Hoch
M
,
Huth
F
,
Sato
M
, et al
.
Pharmacokinetics of asciminib in the presence of CYP3A or P-gp inhibitors, CYP3A inducers, and acid-reducing agents
.
Clin Transl Sci
.
2022
;
15
(
7
):
1698
-
1712
.
You do not currently have access to this content.
Sign in via your Institution