1
UI - 21443827
AU - Soignet SL; Frankel SR; Douer D; Tallman MS; Kantarjian H; Calleja E;
TI -
Stone RM; Kalaycio M; Scheinberg DA; Steinherz P; Sievers EL; Coutre S;
Dahlberg S; Ellison R; Warrell RP Jr
United States multicenter study of arsenic trioxide in relapsed acute
promyelocytic leukemia.
SO - J Clin Oncol 2001 Sep 15;19(18):3852-60
AD - Leukemia and Developmental Chemotherapy Services, Department of
Medicine, Memorial Sloan-Kettering Cancer Center and Joan and Sanford
Weill Medical College of Cornell University, New York, NY 10021, USA.
soignets@mskcc.org
PURPOSE: To determine the safety and efficacy of arsenic trioxide (ATO)
in patients with relapsed acute promyelocytic leukemia (APL). PATIENTS
AND METHODS: Forty patients experiencing first (n = 21) or > or = second
(n = 19) relapse were treated with daily infusions of ATO to a maximum
of 60 doses or until all leukemic cells in bone marrow were eliminated.
Patients who achieved a complete remission (CR) were offered one
consolidation course of ATO that began 3 to 4 weeks later. Patients who
remained in CR were eligible to receive further cycles of ATO therapy on
a maintenance study. RESULTS: Thirty-four patients (85%) achieved a CR.
Thirty-one patients (91%) with CRs had posttreatment cytogenetic tests
negative for t(15;17). Eighty-six percent of the patients who were
assessable by reverse transcriptase polymerase chain reaction converted
from positive to negative for the promyelocytic leukemia/retinoic acid
receptor-alpha transcript by the completion of their consolidation
therapy. Thirty-two patients received consolidation therapy, and 18
received additional ATO as maintenance. Eleven patients underwent
allogeneic (n = 8) or autologous (n = 3) transplant after ATO treatment.
The 18-month overall and relapse-free survival (RFS) estimates were 66%
and 56%, respectively. Twenty patients (50%) had leukocytosis (> 10,000
WBC/microL) during induction therapy. Ten patients developed signs or
symptoms suggestive of the APL syndrome and were effectively treated
with dexamethasone. Electrocardiographic QT prolongation was common
(63%). One patient had an absolute QT interval of > 500 msec and had an
asymptomatic 7-beat run of torsades de pointe. Two patients died during
induction, neither from drug-related causes. CONCLUSION: This study
establishes ATO as a highly effective therapy for patients with relapsed
APL.
2
UI - 21455229
AU - Estey EH
TI -
Therapeutic options for acute myelogenous leukemia.
SO - Cancer 2001 Sep 1;92(5):1059-73
AD - Department of Leukemia, The University of Texas M. D. Anderson Cancer
Center, Houston, Texas 77030-4095, USA. ehestey@mdanderson.org
BACKGROUND: General therapeutic options for patients with acute
myelogenous leukemia (AML) are reviewed and specific new therapies are
described. METHODS: Data in this review came from the published
literature and the M. D. Anderson Cancer Center's acute leukemia
database. RESULTS: Outcome following standard therapy of AML is so
variable that is best to speak of a range of outcomes determined by
various prognostic factors. Therapy can (and usually does) fail because
of treatment-induced mortality or (more usually) resistance to therapy.
Performance status and age are the principal predictors of early death,
whereas cytogenetics, a history of abnormal blood counts, and MDR1
expression are predictors of resistance. Using this information,
physicians can categorize patients into those in whom 1) standard
therapy is indicated, 2) either standard or investigational therapy is
appropriate, and 3) investigational therapy is indicated. The majority
of even newly diagnosed patients belong to Group 3. The availability of
allogeneic or autologous transplantation does not alter this conclusion.
Investigational therapies have been developed that are directed against
the CD33 surface antigen, the multidrug-resistant MDR1 protein, and
other targets. Because of the number of new therapies clinical research
in AML should emphasize pilot trials rather than traditionally large
Phase III studies. CONCLUSIONS: Most patients with newly diagnosed AML
should be offered investigational regimens. Copyright 2001 American
Cancer Society.
3
UI - 21262630
AU - Zhao W; Wang H; Wang X; Wu F; Guo W; Qu B; Shen Z; Wang Z
TI -
Effects of all-trans-retinoic acid and arsenic trioxide on the
hemostatic disturbance associated with acute promyelocytic leukemia.
SO - Thromb Res 2001 May 1;102(3):197-204
AD - Shanghai Institute of Hematology, Rui-Jin Hospital, Shanghai Second
Medical University, 197 Rui Jin Road II, 200025, Shanghai, People's
Republic of China.
To study the in vivo effect of all-trans-retinoic acid (ATRA) and
arsenic trioxide (As(2)O(3)) on the expression of tissue factor (TF) and
the other hemostatic disturbance, a series of parameters were measured
either in bone marrow blasts or plasma from acute promyelocytic leukemia
(APL) patients. The plasma parameters were measured by ELISA or
chromogenic studies. The TF transcription was assessed using reverse
transcription-polymerase chain reaction (RT-PCR) technique. The results
indicated that the blast cell procoagulant activity (PCA), TF antigen of
APL cell lysate, as well as the transcription of APL TF mRNA elevated at
diagnosis, were reduced after ATRA or As(2)O(3) therapy. The plasma
level of P-selectin, TF, thrombin-antithrombin complex (TAT), soluble
fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway
inhibitor (TFPI), plasmin-antiplasmin complex, tissue plasminogen
activator (t-PA) activity, urokinase plasminogen activator (u-PA) and
its receptor (u-PAR), and D-dimer (D-D) significantly increased.
Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG)
activity, alpha(2)-plasminogen inhibitor activity (alpha(2)-PI), and
plasminogen activator inhibitor (PAI) activity were decreased at
diagnosis. The protein C activity (PC:A) and protein S (PS) remained
unchanged. All the parameters were restored to normal ranges after
complete remission (CR) except elevation of TF and TAT in both groups,
as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there
existed activation of platelets and consumption of anticoagulants as
well as activation of coagulation and fibrinolytic system before
treatment. Both ATRA and As(2)O(3) therapy downregulated the expression
of TF mRNA, decreased the PCA and TF level in APL cells, significantly
inhibited coagulation activation, corrected secondary hyperfibrinolysis
and the other hemostatic abnormalities, and thus greatly improved the
bleeding symptom in early stage of the treatment.
4
UI - 21400380
AU - Cesaro S; Meloni G; Messina C; Pillon M; Proglia A; Lanino E; Caniggia
TI -
M; Bagnulo S; Pession A; Locatelli F; Italian Pediatric Group for Bone
Marrow Transplantation
High-dose melphalan with autologous hematopoietic stem cell
transplantation for acute myeloid leukemia: results of a retrospective
analysis of the Italian Pediatric Group for Bone Marrow Transplantation.
SO - Bone Marrow Transplant 2001 Jul;28(2):131-6
AD - Clinica di Oncoematologia Pediatrica, Dipartimento di Pediatria,
Universita di Padova, Italy.
This retrospective study from the Italian Association of Pediatric
Hematology Oncology-Bone Marrow Transplant Group (AIEOP-TMO) reports the
results of consolidation with high-dose melphalan and autologous
hematopoietic stem cell transplantation (auto-HSCT) in patients with
acute myeloid leukemia (AML) in first complete remission (CR1). From
0.11-16.2) were treated in six centers. Eighteen had de novo AML and two
had secondary AML. According to BFM criteria, 10 were classified as
standard- and 10 as high-risk patients, respectively. The median time
from diagnosis to CR1 and from diagnosis to Auto-HSCT were 1.1 months
(range 0.8-1.6) and 4.3 months (range 3.1-6.2), respectively. Purging
with either mafosfamide (three) or in vivo interleukin-2 (four) was
performed in seven of 20 patients. Melphalan was administered at a
dosage of 150-220 mg/m(2) (median 180). Median total number of nucleated
cells infused was 2.5 x 10(8)/kg (range 1.1-8.9). The myeloablative
regimen was well tolerated with no toxic death, veno-occlusive disease
or life-threatening complications. All patients had hematopoietic
recovery in a median time of 27 days for neutrophils and 44 days for
platelets. Eight of 20 patients relapsed after a median time of 7.2
months from transplant (range 5.7-15.9). Six of them died (five of
progression of disease and one of sepsis) while the remaining two
patients are alive in CR2. The 3-year cumulative probability of survival
and event-free-survival (EFS) is 62% and 56%, respectively. This study
showed that in pediatric patients with AML consolidation of CR1 with
high-dose melphalan allows survival and EFS to be obtained comparable to
other auto-HSCT or chemotherapy published series with a potential
sparing effect both on duration of treatment (with respect to
chemotherapy) and on long-term side-effects (with respect to auto-HSCT
with TBI or busulfan containing regimens).
5
UI - 21437188
AU - Mansson E; Paul A; Lofgren C; Ullberg K; Paul C; Eriksson S; Albertioni
TI -
F
Cross-resistance to cytosine arabinoside in a multidrug-resistant human
promyelocytic cell line selected for resistance to doxorubicin:
implications for combination chemotherapy.
SO - Br J Haematol 2001 Sep;114(3):557-65
AD - Department of Medicine, Division of Clinical Pharmacology, Karolinska
Hospital, Stockholm, Sweden.
The pyrimidine analogue cytosine arabinoside (AraC) is one of the most
effective drugs used in the treatment of acute leukaemia. Overexpression
of the multidrug resistance (MDR-1) gene and its product, P-glycoprotein
(P-gp), is associated with cellular resistance to drugs, such as
anthracyclines and vinca alkaloids. This resistance can be reversed by
cyclosporine analogues or verapamil (ver). We investigated the in vitro
cross-resistance to AraC in a doxorubicin-resistant HL60 cell line, with
an elevated expression of the MDR-1 gene. The resistant clone showed an
eightfold increased resistance to AraC and a two- to fourfold resistance
to the other analogues, as measured by cytotoxicity test. There was no
significant increase in the activity of 5'-nucleotidase or in the amount
of deoxyribonucleotide pools between cell lines. We could, however,
detect a reduction in deoxycytidine kinase (dCK) activity (30%, P =
0.021, using deoxycytidine as substrate) and the level of AraC
triphosphates was significantly reduced in the resistant cells (70%, P =
0.009). When the cells were exposed to cyclosporin A (CsA) or the
cyclosporine analogue PSC 833 (PSC) in combination with AraC, there was
more extensive apoptosis, as measured by formation of oligonucleosomal
DNA fragmentation and caspase-3-like activity, than with exposure to
AraC alone. We also found an increased retention of AraC in the
resistant cells when incubated with AraC in combination with CsA. Ver in
combination with AraC, failed to increase apoptosis for the resistant
cell line. Our data suggests that the resistance to AraC for the
P-gp-expressing cells is a result of a reduction of dCK activity and an
increase in efflux, the latter possibly depending on P-gp. A combination
of CsA or PSC with AraC may improve the effect of AraC in vivo.
6
UI - 21463157
AU - Au WY; Chan GC; Chim CS; Shek TW; Ooi GC; Ho WK; Kwong YL
TI -
Unusual sites of involvement by hematologic malignancies. Case 3.
External auditory canal tumor: a rare chloroma in acute promyelocytic
leukemia with a complete response to arsenic trioxide.
SO - J Clin Oncol 2001 Oct 1;19(19):3993-5
AD - Queen Mary Hospital, Hong Kong.
7
UI - 21471001
AU - Asou N; Adachi K; Tamura U; Kanamaru A; Kageyama S; Hiraoka A; Omoto E;
TI -
Akiyama H; Tsubaki K; Saito K; Kuriyama K; Oh H; Kitano K; Miyawaki S;
Takeyama U; Yamada O; Nishikawa K; Takahashi M; Matsuda S; Ohtake H;
Ohno R
Analysis of prognostic factors in newly diagnosed patients with acute
promyelocytic leukemia: the APL92 study of the Japan Adult Leukemia
Study Group (JALSG).
SO - Cancer Chemother Pharmacol 2001 Aug;48 Suppl 1():S65-71
AD - Second Department of Internal Medicine, Kumamoto University School of
Medicine, Honjo, Japan. ktcnasou@kaiju.medic.kumamoto-u.ac.jp
All-trans-retinoic acid (ATRA) has been incorporated in front-line
therapy for newly diagnosed acute promyelocytic leukemia (APL). We
conducted a multicenter study of differentiation therapy with ATRA alone
or in combination with chemotherapy followed by intensive postremission
chemotherapy in patients with APL (the JALSG APL92 study), and analyzed
prognostic factors to increase the cure rate in our subsequent trial.
From 1992 to 1997, adult patients with newly diagnosed APL received oral
ATRA 45 mg/m2 daily alone until complete remission (CR) if initial
leukocyte counts were < 3.0x10(9)/l, and ATRA daily plus daunorubicin
(DNR) 40 mg/m2x3 days plus enocitabine (BHAC) 200 mg/m2x5 days if
leukocyte counts were > or =3.0 x 10(9)/l. If peripheral blasts exceeded
1.0x10(9)/l during therapy, DNRx3 days plus BHACx5 days was added. After
CR was achieved, three courses of consolidation and six courses of
maintenance/intensification chemotherapy were administered. Of 376
patients enrolled, 369 were evaluable (median age 46 years, range 15-86
years; median leukocyte counts 2.0x10(9)/l), and 333 (90%) achieved CR
(94% of patients treated with ATRA alone, 88% with ATRA plus later
chemotherapy, 89% with ATRA plus initial chemotherapy, and 86% with ATRA
plus initial and later chemotherapy). At a median follow-up of 45
months, the predicted 6-year overall and event-free survival (EFS) rates
for all patients were 65% and 52%, respectively. Favorable prognostic
factors for CR were younger age, no or mild purpura, high serum total
protein level, low lactate dehydrogenase level, and no or mild
disseminated intravascular coagulation (DIC). Favorable prognostic
factors for EFS were leukocyte counts < 10.0x10(9)/l, mild DIC, and no
sepsis during induction therapy. In the JALSG APL97 study, we
intensified chemotherapy for patients with leukocyte counts > or
=3.0x10(9)/l, and are randomly testing whether further chemotherapy is
required for APL patients with negative PCR for PML/retinoic acid
receptor alpha in the maintenance phase.
8
UI - 21471002
AU - Wang ZY
TI -
Arsenic compounds as anticancer agents.
SO - Cancer Chemother Pharmacol 2001 Aug;48 Suppl 1():S72-6
AD - Shanghai Institute of Hematology, Rui-jin Hospital, Shanghai Second
Medical University, People's Republic of China.
In this paper the use of arsenic compounds as anticancer agents in
clinical trials and in in vitro investigations is reviewed, including
the experience at our institute. Treatment of newly diagnosed and
relapsed patients with acute promyelocytic leukemia (APL) with arsenic
trioxide (As2O3) has been found to result in complete remission (CR)
rates of 85-93% when given by intravenous infusion for 2-3 h at a dose
of 10 mg/day diluted in 5% glucose saline solution. Patients exhibit a
response in 28-42 days. CR rates after administration of Composite
Indigo Naturalis tablets containing arsenic sulfide and of pure
tetraarsenic tetrasulfide reached 98% and 84.9%, respectively. At higher
concentrations (1-2 microM), arsenic induced apoptosis, while at lower
concentrations (0.1-0.5 microM), it triggered cell differentiation in
vitro. As2O3-induced apoptosis has been observed in many cancer cell
lines, including esophageal carcinoma, gastric cancer, neuroblastoma,
lymphoid malignancies, and multiple myeloma. Its effectiveness was
confirmed in the treatment of multiple myeloma. Arsenic compounds are
effective agents in the treatment of APL and their activity against
other types of cancer requires further investigation.
9
UI - 21284538
AU - Okamoto Y; Tsuda T; Matsunami M; Hirose T; Sakaguchi R; Katayama N; Ota
TI -
K
Treatment of acute myeloblastic leukaemia in a patient with Bombay blood
type: a case report.
SO - J Int Med Res 2001 Mar-Apr;29(2):140-6
AD - Department of Blood Transfusion Medicine and Clinical Haematology,
Wakayama Medical College, Wakayama City, Japan.
yokamoto@wakayama-med.ac.jp
A 62-year-old female was admitted to our hospital with suspected acute
leukaemia and after investigation we diagnosed acute myeloblastic
leukaemia (AML-M1). The patient's blood type was found to be the very
rare Bombay type and surveillance of her relatives showed the same blood
type in her male cousin on her mother's side. Alongside chemotherapy the
patient received 4000 ml of frozen Bombay-type red cells, 1400 ml of
concentrated red cells in manitol adenine phosphate solutions and 360
units of type O concentrated platelets without marked effects. The
anti-H antibody was initially at 128 dilution but for unknown reasons
increased to 2048 dilution after remission of AML-M1. About 3 months
after hospitalization the patient died of Cryptococcus neoformans
pneumonia despite strict precautions against infection. Although AML-M1
is a common adult leukaemia and is chemosensitive to anti-leukaemic
drugs, neither AML-M1 in a patient with Bombay-type red cells nor its
treatment with chemotherapy and transfusion with type Oh frozen red
cells have previously been reported.
10
UI - 21346270
AU - Takeshita A
TI -
[Prognostic factors and treatment of acute myelogenous leukemia based on
clinical results obtained by the Japan Adult Leukemia Study Group]
SO - Rinsho Ketsueki 2001 May;42(5):366-71
11
UI - 21346273
AU - Sakura T
TI -
[Indications for allogeneic bone marrow transplantation (BMT) in adult
acute myelogenous leukemia: matched-pair analysis in comparison with
chemotherapy in patients achieving initial remission]
SO - Rinsho Ketsueki 2001 May;42(5):380-4
12
UI - 21371225
AU - Ma R; Liu F; Yang J
TI -
[Clinical study on effect of Fuzheng Kangbai Granule on long-term
survival of patients with acute leukemia]
SO - Zhongguo Zhong Xi Yi Jie He Za Zhi 1998 May;18(5):276-8
AD - Department of Hematology, Xiyuan Hospital, China Academy of TCM, Beijing
100091.
OBJECTIVE: To observe the effect of Fuzheng Kangbai Granule (FZKBG) on
event free interval (EFI) and over survival (OS) of patients with acute
leukemia, and to study the mechanism of FZKBG. METHODS: FZKBG was used
in 90 cases of completely remitted acute leukemia, immune functions of
patients before and after using FZKBG were measured. RESULTS: Five year
EFI and OS were 64.2% and 77.2% of 90 cases of completely remitted acute
leukemia, and the immune functions after using FZKBG have improved
significantly. CONCLUSIONS: FZKBG could increase the EFI and OS of
patients with acute leukemia, and the improved immune functions may play
a role in increasing 5 year EFI and OS.
13
UI - 21430352
AU - Mathews V; Chandy M; Srivastava A
TI -
Arsenic trioxide in the management of acute promyelocytic leukaemia.
SO - Natl Med J India 2001 Jul-Aug;14(4):215-22
AD - Department of Haematology, Christian Medical College and Hospital,
Vellore 632004, Tamil Nadu, India. vikrammathews@hotmail.com
Arsenical compounds were used as early as 2000 BC, both as medicines as
well as poisons. Arsenicals gained importance in the beginning of the
last century as the primary mode of treating syphilis. In 1931, Folkner
and Scott used an arsenical preparation called Fowler's solution in the
treatment of chronic myeloid leukaemia. This continued to be used until
the introduction of busulphan in 1953. In the 1970s, arsenic trioxide
was introduced for the treatment of acute promyelocytic leukaemia in
China and was found to be extremely effective in treating this
condition. Since then, numerous in vitro and in vivo studies have
confirmed this observation. This article reviews the pathogenesis of
acute promyelocytic leukaemia, the possible mechanism of action of
arsenic trioxide in this condition and the literature on its use in the
treatment, with special reference to the clinical and molecular response
rates, toxicity and pharmacology of this compound. It also attempts to
address the role of arsenic trioxide in the present algorithm for the
treatment of acute promyelocytic leukaemia.
14
UI - 90331661
AU - Rhodes AM
TI -
A minor's refusal of treatment.
SO - MCN Am J Matern Child Nurs 1990 Jul-Aug;15(4):261
AD - Finance and University Services, University of Iowa, Iowa City.
15
UI - 91014412
AU - Cullis JO; Smith AG
TI -
Jehovah's Witnesses with leukaemia.
SO - Lancet 1990 Oct 27;336(8722):1075-6
16
UI - 91244595
AU - Salyer DR
TI -
In re E.G., a minor.
SO - Issues Law Med 1991 Spring;6(4):421-4
17
UI - 97393802
AU - Kerridge I; Lowe M; Seldon M; Enno A; Deveridge S
TI -
Clinical and ethical issues in the treatment of a Jehovah's Witness with
acute myeloblastic leukemia.
SO - Arch Intern Med 1997 Aug 11-25;157(15):1753-7
AD - Health Law and Ethics Program, University of Newcastle, Australia.
We report the first documented case of the use of peripheral blood stem
cell autografting in the treatment of a Jehovah's Witness with acute
myeloblastic leukemia. This case illustrates the complex ethical and
clinical issues that arise in the treatment of such patients.
18
UI - 21291607
AU - Colita A; Belhabri A; Chelghoum Y; Charrin C; Fiere D; Thomas X
TI -
Prognostic factors and treatment effects on survival in acute myeloid
leukemia of M6 subtype: a retrospective study of 54 cases.
SO - Ann Oncol 2001 Apr;12(4):451-5
AD - Service d'Hematologie, Hjpital Edouard Herriot, Lyon, France.
classification system of acute myeloid leukemia (AML) which designates
it as M6 AML. This report describes the data of 54 patients with newly
Median age was 59 years. Pancytopenia was the most common feature at
diagnosis. Twenty-six percent of cases presented with secondary AML.
Karyotype was successfully performed in 35 cases. Eleven patients
presented with normal karyotype, nine with simple karyotypic
abnormalities, and fifteen with major karyotypic abnormalities. Fifty of
the fifty-four patients received one or two courses of induction
chemotherapy combining anthracyclines with cytarabine according to
different successive protocols. One elderly patient only received
low-dose cytarabine, and three patients died before any chemotherapy
could be given. RESULTS: Complete remission (CR) was achieved in 29
cases (54%, 95% confidence interval (CI): 40%-67%). As post-remission
therapy, four patients could be allografted, and two underwent
autologous transplantation. All other treated patients received
continuation chemotherapy. Twenty-one patients have relapsed (72%).
Median time to relapse was six months. Among those patients, only eight
achieved a second CR (38%). The median disease-free survival (DFS) was
eight months (95% CI: 4-10 months) with a five-year survival rate of
17%. Median overall survival (OS) was nine months (95% CI: 5-12 months)
with a five-year survival rate of 13%. In univariate analysis, poor
prognostic factors for DFS were secondary AML (P = 0.05) and initial
platelet count <50 x 109/l (P = 0.02). Poor prognostic factors for OS
were age > or = 60 years (P = 0.005), secondary AML (P = 0.05), initial
'blastic' fever (P = 0.0004), and initial haemoglobin level < 90 g/l (P
= 0.03). All factors, but haemoglobin level, remained significant in the
multivariate analysis. Although it was not statistically significant,
there was a trent for a better prognosis of M6 patients presenting with
normal karyotype as compared to those displaying chromosomal
abnormality. CONCLUSIONS: This retrospective analysis points to a
somewhat heterogenous group of AML in terms of clinical and biological
features, and outcome. Distinctive subgroups can be identified according
to prognostic factors related to survival. A larger multicenter study
with well-defined diagnostic criteria is warranted to further clarify
treatment effects.
19
UI - 21445089
AU - Milella M; Kornblau SM; Estrov Z; Carter BZ; Lapillonne H; Harris D;
TI -
Konopleva M; Zhao S; Estey E; Andreeff M
Therapeutic targeting of the MEK/MAPK signal transduction module in
acute myeloid leukemia.
SO - J Clin Invest 2001 Sep;108(6):851-9
AD - Department of Blood and Marrow Transplantation, Section of Molecular
Hematology and Therapy, The University of Texas, M.D. Anderson Cancer
Center, Houston, Texas 77030, USA.
The mitogen-activated protein kinase (MAPK) pathway regulates growth and
survival of many cell types, and its constitutive activation has been
implicated in the pathogenesis of a variety of malignancies. In this
study we demonstrate that small-molecule MEK inhibitors (PD98059 and
PD184352) profoundly impair cell growth and survival of acute myeloid
leukemia (AML) cell lines and primary samples with constitutive MAPK
activation. These agents abrogate the clonogenicity of leukemic cells
but have minimal effects on normal hematopoietic progenitors. MEK
blockade also results in sensitization to spontaneous and drug-induced
apoptosis. At a molecular level, these effects correlate with modulation
of the expression of cyclin-dependent kinase inhibitors (p27(Kip1) and
p21(Waf1/CIP1)) and antiapoptotic proteins of the inhibitor of apoptosis
proteins (IAP) and Bcl-2 families. Interruption of constitutive MEK/MAPK
signaling therefore represents a promising therapeutic strategy in AML.
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