Treatment with all-trans retinoic acid in acute promyelocytic leukemia reduces early deaths in children

Mann, Georg; Reinhardt, Dirk; Ritter, J.; Hermann, Johannes C.; Schimrigk, К.; Gadner, Helmut; Creutzig, Ursula

doi:10.1007/s002770100304

Cited by 94 publications

(82 citation statements)

References 15 publications

(12 reference statements)

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“…Treatment with As 2 O 3 achieves remission rates of more than 90%, which is similar to data from children treated with ATRA and chemotherapy. 2,3 There is however no data regarding the use of As 2 O 3 as primary therapy in children. Ma Jun et al in their study of 62 children with relapsed APML showed remission rates of 81% with a 7-year DFS of 65% (Blood 2001; abstract 3119).…”

Section: Discussionmentioning

confidence: 99%

“…1 The frontline therapy for APML using a combination of ATRA and chemotherapy has shown initial remission rates of 69-97% with event-free survival (EFS) ranging between 64 and 77% in studies from various countries including India. [2][3][4][5][6] Treatment with ATRA, however, is not financially possible for all patients in economically poor countries and hence alternative therapeutic strategies have been explored. Arsenic trioxide (As 2 O 3 ) was initially used in the treatment of relapsed APML with remission rates of 80-90% and long-term DFS of 60-80%.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of children with newly diagnosed acute promyelocytic leukemia with arsenic trioxide: a single center experience

et al. 2004

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A total of 11 children (five males and six females) with hypergranular type of acute promyelocytic leukemia (APML) were treated with intravenous arsenic trioxide (As 2 O 3 ) between December 1998 and October 2003. Eight cycles of As 2 O 3 (0.15 mg/kg/day) were administered (induction, consolidation and six cycles of maintenance) over a period of 12 months. The median WBC count at diagnosis was 3400/mm 3 (range: 800-9800). In all, 10 patients (91%) achieved hematological remission at a mean duration of 48 days (range: 41-60) with all 10 patients achieving molecular remission at a median duration of 81 days (range: 64-109). Toxicity was minimal with leukocytosis in six patients, ichthyosis and hyperpigmentation of skin in five and mild peripheral neuropathy in one patient. One patient who relapsed 6 months after completing therapy achieved a second hematological and molecular remission with As 2 O 3 . With a median follow-up of 30 months (range: 4-62), the overall (OS) survival is 91% with a relapse-free survival (RFS) of 81%. As 2 O 3 achieves hematological and molecular remission in majority of newly diagnosed children with APML with minimal toxicity, but long-term follow-up is required to evaluate late effects of As 2 O 3 and study the minimum dose and duration required for a sustained remission.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treatment of children with newly diagnosed acute promyelocytic leukemia with arsenic trioxide: a single center experience

et al. 2004

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“…For patients with acute promyelocytic leukemia, the early death rate due to coagulopathy has dropped significantly with the introduction of all-trans-retinoic acid. 27 The death in CR rate in AML increased to an unacceptably high level (15.3%) in study AML-92/94. This contributed to the slightly inferior overall survival when study AML-92/94 was compared with AML-87.…”

Section: Discussionmentioning

confidence: 99%

Causes of death – other than progressive leukemia – in childhood acute lymphoblastic (ALL) and myeloid leukemia (AML): the Dutch Childhood Oncology Group experience

et al. 2005

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We analyzed causes of death, other than resistant disease or relapse, in 875 children with acute lymphoblastic leukemia (ALL) and 229 with acute myeloid leukemia (AML), treated on three different Dutch Childhood Oncology Group (DCOG) ALL and three AML protocols. Overall, 23 (2.6%) ALL and 44 (19.2%) AML patients died. Early death (ED, before remission was reached) occurred in nine ALL (1%) and thirty AML (13.1.%) patients, including three and ten deaths before treatment was initiated. Chemotherapy-related mortality in remission (CRM) occurred in nine ALL (1.1%) and eight AML (4.4%) patients. For ALL, both ED and CRM declined over time, although this was not statistically significant. For AML a decrease in ED was observed (from 26% to approximately 10%), but counterbalanced by an increase in CRM (from 3 to 8%), maybe related to the scheduling of intensification blocks in AML-92/94. Including transplant-related mortality, death in CR rates in AML increased from 3 to 15% in the last study. The main cause of ED was hemorrhage, often associated with hyperleucocytosis, and infection for CRM. We conclude that mortality dropped favorably in ALL, but not in AML. Especially for AML, effective but less toxic therapy and better supportive care guidelines need to be developed.

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“…The HL-60 cell line was established from peripheral blood leukocytes of a patient originally diagnosed with acute promyelocytic leukemia (4), which was retrospectively re-evaluated to be acute myeloblastic leukemia (7). HL-60 cells undergo G 0 cell cycle arrest and myeloid differentiation in response to RA or monocytic differentiation in response to 1,25-dihydroxyvitamin D 3 . Induced differentiation depends on hyperactive MAPK signaling (1,8).…”

mentioning

confidence: 99%

c-Cbl Tyrosine Kinase-binding Domain Mutant G306E Abolishes the Interaction of c-Cbl with CD38 and Fails to Promote Retinoic Acid-induced Cell Differentiation and G0 Arrest

Shen

Yen

2009

Journal of Biological Chemistry

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Retinoic acid (RA) causes HL-60 human myeloblastic leukemia cell myeloid differentiation that is dependent on MAPK signaling. The process is propelled by c-Cbl, which binds the CD38 receptor as part of a signaling complex generating MAPK signaling. Here we report that the capability of c-Cbl to do this is lost in the G306E tyrosine kinase-binding domain mutant. Retinoic acid (RA), 2 a form of vitamin A, can cause activation of MAPK signaling leading to induced cell differentiation and G 0 cell cycle arrest (1-2). Because of this, RA has been used therapeutically for the chemoprevention and treatment of cancer (3), notably acute promyelocytic leukemia, making its mechanism of action of significant interest. The HL-60 human myeloblastic leukemia cell line serves as a model for studying differentiation induction therapy and the mechanism of RA action (4 -6). The HL-60 cell line was established from peripheral blood leukocytes of a patient originally diagnosed with acute promyelocytic leukemia (4), which was retrospectively re-evaluated to be acute myeloblastic leukemia (7). HL-60 cells undergo G 0 cell cycle arrest and myeloid differentiation in response to RA or monocytic differentiation in response to 1,25-dihydroxyvitamin D 3 . Induced differentiation depends on hyperactive MAPK signaling (1, 8). c-Cbl contributes propulsion to this process (9, 10). It is part of a signaling complex connected to the CD38 receptor that activates the RAF/MEK/ ERK MAPK signaling axis to drive differentiation and G 0 cell cycle arrest (9).The 120-kDa product of the c-Cbl protooncogene is a prominent component of tyrosine kinase signaling cascades downstream of activated cell surface receptors, including the epidermal growth factor receptor, the B cell receptor, Fc receptor, and cytokine receptors (11,12). Cbl proteins have a highly conserved N-terminal domain termed the tyrosine kinase-binding (TKB) domain, which binds to phosphotyrosines on activated receptor-tyrosine kinases and other signaling proteins (13, 14), a short linker region, and a Ring finger domain that binds to ubiquitin-conjugating enzymes (15, 16). The Ring finger domain of c-Cbl presents the most conserved region among Cbl family proteins, and it is implicated as an important element in the function of Cbl proteins (17)(18)(19). The TKB domain contains a four-helix bundle, EF-hand calcium-binding domain, and a variant SH2 domain that binds to phosphotyrosine residues (13,20). Several features of the Cbl/Zap-70 complex (13) suggest that the four-helix bundle, EF-hand, and SH2 domains together form an interactive structure that is crucial for phosphoprotein recognition. Studies by Thien et al. (21) indicated that the TKB mutation, G306E, fails to bind phosphotyrosine residues and is a loss of function mutation in the c-Cbl TKB domain.Cbl interacts with a number of intracellular signaling molecules including various receptors, adaptors, cytoskeletal proteins, ubiquitin, and structural proteins via its various domains (22,23). One of the receptors is CD38. The human c...

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Treatment with all-trans retinoic acid in acute promyelocytic leukemia reduces early deaths in children

Cited by 94 publications

References 15 publications

Treatment of children with newly diagnosed acute promyelocytic leukemia with arsenic trioxide: a single center experience

Treatment of children with newly diagnosed acute promyelocytic leukemia with arsenic trioxide: a single center experience

Causes of death – other than progressive leukemia – in childhood acute lymphoblastic (ALL) and myeloid leukemia (AML): the Dutch Childhood Oncology Group experience

c-Cbl Tyrosine Kinase-binding Domain Mutant G306E Abolishes the Interaction of c-Cbl with CD38 and Fails to Promote Retinoic Acid-induced Cell Differentiation and G0 Arrest

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