Abstract
We report on the antileukemic activity of homoharringtonine (HHT) in T-cell acute lymphoblastic leukemia (T-ALL). We showed that HHT inhibited the NOTCH/MYC pathway and induced significantly longer survival in mouse and patient-derived T-ALL xenograft models, supporting HHT as a promising agent for T-ALL.
References
1.
Van Vlierberghe
P
, Ferrando
A
. The molecular basis of T cell acute lymphoblastic leukemia
. J Clin Invest
. 2012
;122
(10
):3398
-3406
.2.
Lonetti
A
, Cappellini
A
, Bertaina
A
, et al. Improving nelarabine efficacy in T cell acute lymphoblastic leukemia by targeting aberrant PI3K/AKT/mTOR signaling pathway
. J Hematol Oncol
. 2016
;9
(1
):114
.3.
Lu
S
, Wang
J
. Homoharringtonine and omacetaxine for myeloid hematological malignancies
. J Hematol Oncol
. 2014
;7
:2
.4.
Nazha
A
, Kantarjian
H
, Cortes
J
, Quintas-Cardama
A
. Omacetaxine mepesuccinate (synribo) - newly launched in chronic myeloid leukemia
. Expert Opin Pharmacother
. 2013
;14
(14
):1977
-1986
.5.
Li
C
, Dong
L
, Su
R
, et al. Homoharringtonine exhibits potent anti-tumor effect and modulates DNA epigenome in acute myeloid leukemia by targeting SP1/TET1/5hmC
. Haematologica
. 2020
;105
(1
):148
-160
.6.
Chen
R
, Guo
L
, Chen
Y
, Jiang
Y
, Wierda
WG
, Plunkett
W
. Homoharringtonine reduced Mcl-1 expression and induced apoptosis in chronic lymphocytic leukemia
. Blood
. 2011
;117
(1
):156
-164
.7.
Kantarjian
HM
, Talpaz
M
, Smith
TL
, et al. Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia
. J Clin Oncol
. 2000
;18
(20
):3513
-3521
.8.
Gurel
G
, Blaha
G
, Moore
PB
, Steitz
TA
. U2504 determines the species specificity of the A-site cleft antibiotics: the structures of tiamulin, homoharringtonine, and bruceantin bound to the ribosome
. J Mol Biol
. 2009
;389
(1
):146
-156
.9.
Chen
XJ
, Zhang
WN
, Chen
B
, et al. Homoharringtonine deregulates MYC transcriptional expression by directly binding NF-kappaB repressing factor
. Proc Natl Acad Sci U S A
. 2019
;116
(6
):2220
-2225
.10.
Langenau
DM
, Traver
D
, Ferrando
AA
, et al. Myc-induced T cell leukemia in transgenic zebrafish
. Science
. 2003
;299
(5608
):887
-890
.11.
Smith
DP
, Bath
ML
, Metcalf
D
, Harris
AW
, Cory
S
. MYC levels govern hematopoietic tumor type and latency in transgenic mice
. Blood
. 2006
;108
(2
):653
-661
.12.
Roderick
JE
, Tesell
J
, Shultz
LD
, et al. c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells
. Blood
. 2014
;123
(7
):1040
-1050
.13.
King
B
, Trimarchi
T
, Reavie
L
, et al. The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability
. Cell
. 2013
;153
(7
):1552
-1566
.14.
Herranz
D
, Ambesi-Impiombato
A
, Palomero
T
, et al. A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia
. Nat Med
. 2014
;20
(10
):1130
-1137
.15.
DeAngelo
DJ
, Yu
D
, Johnson
JL
, et al. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801
. Blood
. 2007
;109
(12
):5136
-5142
.16.
Teachey
DT
, Devidas
M
, Wood
BL
, et al. Children's Oncology Group trial AALL1231: a phase III clinical trial testing bortezomib in newly diagnosed T-cell acute lymphoblastic leukemia and lymphoma
. J Clin Oncol
. 2022
;40
(19
):2106
-2118
.17.
Bride
KL
, Vincent
TL
, Im
SY
, et al. Preclinical efficacy of daratumumab in T-cell acute lymphoblastic leukemia
. Blood
. 2018
;131
(9
):995
-999
.18.
Chonghaile
TN
, Roderick
JE
, Glenfield
C
, et al. Maturation stage of T-cell acute lymphoblastic leukemia determines BCL-2 versus BCL-XL dependence and sensitivity to ABT-199
. Cancer Discov
. 2014
;4
(9
):1074
-1087
.19.
Ferrando
AA
. The role of NOTCH1 signaling in T-ALL
. Hematology Am Soc Hematol Educ Program
. 2009
;2009
(1
):353
-361
.20.
Liu
Y
, Easton
J
, Shao
Y
, et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia
. Nat Genet
. 2017
;49
(8
):1211
-1218
.21.
Sanchez-Martin
M
, Ferrando
A
. The NOTCH1-MYC highway toward T-cell acute lymphoblastic leukemia
. Blood
. 2017
;129
(9
):1124
-1133
.22.
Rodriguez
S
, Abundis
C
, Boccalatte
F
, et al. Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL
. Leukemia
. 2020
;34
(5
):1241
-1252
.23.
Carlesso
N
, Aster
JC
, Sklar
J
, Scadden
DT
. Notch1-induced delay of human hematopoietic progenitor cell differentiation is associated with altered cell cycle kinetics
. Blood
. 1999
;93
(3
):838
-848
.© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
2024
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