☆ 4.6 Review

Molecular-Targeted Therapy of Pediatric Acute Myeloid Leukemia

MOLECULES (2022)

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Article Hematology

Decitabine and vorinostat with FLAG chemotherapy in pediatric relapsed/refractory AML: Report from the therapeutic advances in childhood leukemia and lymphoma (TACL) consortium

Lauren Pommert et al.

Summary: The combination of Decitabine and Vorinostat with FLAG showed promising efficacy in treating pediatric patients with R/R AML, especially those with epigenetic alterations. The therapy was well-tolerated and effective, with a significant proportion of patients achieving complete response and MRD negativity, leading to successful hematopoietic stem cell transplant. Correlative pharmacodynamics studies also revealed the biological activity of the drugs and identified specific gene enrichment signatures in nonresponding patients.

AMERICAN JOURNAL OF HEMATOLOGY (2022)

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Article Hematology

Decitabine combined with minimally myelosuppressive therapy for induction of remission in pediatric high-risk acute myeloid leukemia with chromosome 5q deletion: a report of three cases

Shengqin Cheng et al.

Summary: Cases of pediatric acute myeloid leukemia (AML) with complex karyotypes including chromosome 5 abnormalities are rare and have a very poor prognosis. This study shows that combination therapy can effectively induce remission with good tolerability and improve survival rates in this subtype of AML patients.

INTERNATIONAL JOURNAL OF HEMATOLOGY (2022)

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Review Medicine, General & Internal

Pediatric Acute Myeloid Leukemia-Past, Present, and Future

Dirk Reinhardt et al.

Summary: This review discusses the key developments in pediatric acute myeloid leukemia (AML) in terms of diagnosis, treatment, risk groups, and outcomes. It also provides a brief overview of current and future approaches.

JOURNAL OF CLINICAL MEDICINE (2022)

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Article Oncology

First-in-human study of WT1 recombinant protein vaccination in elderly patients with AML in remission: a single-center experience

Stefanie Kreutmair et al.

Summary: This article reports the results of a clinical trial using WT1 recombinant protein vaccination therapy in five elderly AML patients. Clinical benefit was observed in three patients, suggesting the potential efficacy of this treatment method for AML patients.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2022)

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Review Biochemistry & Molecular Biology

Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia

Seiichiro Katagiri et al.

Summary: This paper discusses the role of KIT mutations and the potential of precision medicine in acute myeloid leukemia (AML). New therapies targeting KIT mutations show promise as effective treatments for AML.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Biology

BiTEs, DARTS, BiKEs and TriKEs-Are Antibody Based Therapies Changing the Future Treatment of AML?

Cecily Allen et al.

Summary: After nearly four decades since their conceptualization, antibody-based therapies are slowly being integrated into the treatment of acute myeloid leukemia (AML). While gemtuzumab ozogamicin is the only approved antibody-based therapy for AML thus far, the development of bispecific antibodies has shown early promising results, with the common concept of simultaneous binding to malignant cell surface targets and CD3 on T cells.

LIFE-BASEL (2021)

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Article Oncology

Decitabine Induces Gene Derepression on Monosomic Chromosomes: In Vitro and In Vivo Effects in Adverse-Risk Cytogenetics AML

Gabriele Greve et al.

Summary: This study investigated the therapeutic effects of hypomethylating agents on patients with acute myeloid leukemia/myelodysplastic syndrome, revealing that these agents can derepress genes in AML with chromosomal deletions and reactivate endogenous retroviruses, leading to improved survival rates for patients.

CANCER RESEARCH (2021)

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Review Oncology

Insights into the molecular profiles of adult and paediatric acute myeloid leukaemia

Myint Myat Khine Aung et al.

Summary: AML is a heterogeneous disease characterized by uncontrolled proliferation of hematopoietic stem and myeloid progenitor cells. It accounts for 20% of all leukemias in children and has many similarities between pediatric and adult AML, although characteristics can vary with age of onset. Molecular profiling offers avenues for studying prognostic biomarkers and targetable vulnerabilities.

MOLECULAR ONCOLOGY (2021)

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Review Biochemistry & Molecular Biology

Emerging Immunotherapy for Acute Myeloid Leukemia

Rikako Tabata et al.

Summary: Studies have suggested the potential clinical benefits of immuno-oncology therapy against AML, including immune checkpoint inhibitors and bi-/tri-specific antibodies. CAR-T and NK cells have shown effectiveness for relapsed/refractory AML patients, and conventional chemotherapy combined with anti-PD-1/anti-CTLA4 antibodies also demonstrated certain efficacy.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Oncology

Sorafenib or placebo in patients with newly diagnosed acute myeloid leukaemia: long-term follow-up of the randomized controlled SORAML trial

Christoph Roellig et al.

Summary: The addition of sorafenib to standard chemotherapy in newly diagnosed AML patients led to a significant improvement in event-free and relapse-free survival, although the overall survival benefit did not reach statistical significance. The results confirm the anti-leukemic activity of sorafenib.

LEUKEMIA (2021)

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Review Pharmacology & Pharmacy

Targeting RUNX1 in acute myeloid leukemia: preclinical innovations and therapeutic implications

Fanny Gonzales et al.

Summary: RUNX1 is a crucial transcription factor in normal and malignant hematopoiesis, with potential as a therapeutic target in AML. Recent advancements in targeting RUNX1 have shown promising anti-leukemic effects in preclinical models. Further research into the molecular mechanisms and downstream pathways of RUNX1 in AML development may lead to more precise and efficient therapies.

EXPERT OPINION ON THERAPEUTIC TARGETS (2021)

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Article Oncology

Impact of KMT2A Rearrangement and CSPG4 Expression in Pediatric Acute Myeloid Leukemia

Lina Marie Hoffmeister et al.

Summary: KMT2A rearrangements are common in pediatric AML and are important for risk group stratification. This study analyzed a cohort of 967 pediatric AML patients, finding no impact of KMT2A-r on overall survival when subgroups were combined, but showing different prognosis in various subgroups. KMT2A-r is correlated with KRAS mutations and has less FLT3-ITDs, while being mutually exclusive with other genetic mutations. Additionally, CSPG4 expression is correlated with KMT2A-r but does not have a significant prognostic impact.

CANCERS (2021)

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Review Oncology

IDH Inhibitors in AML-Promise and Pitfalls

Hannah McMurry et al.

Summary: Mutations in IDH1 and IDH2 are common in AML, with inhibitors of these mutated genes now approved by the FDA for AML treatment. While IDH inhibitors show efficacy as monotherapy, they demonstrate higher response rates when combined with HMAs. Current and future trials are exploring various combination approaches, such as with standard chemotherapy, maintenance therapy, and venetoclax-based regimens, to optimize outcomes for AML patients with IDH mutations.

CURRENT HEMATOLOGIC MALIGNANCY REPORTS (2021)

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Article Genetics & Heredity

Cytogenetic and mutational analysis and outcome assessment of a cohort of 284 children with de novo acute myeloid leukemia reveal complex karyotype as an adverse risk factor for inferior survival

Xi Chen et al.

Summary: The study on 284 Chinese children with de novo AML revealed that complex karyotype (CK) is an adverse risk factor for reduced survival, with CK-AML patients showing shorter overall survival and event-free survival. Additionally, typical CK and a higher number of cytogenetic aberrations were associated with poorer outcomes in childhood AML.

MOLECULAR CYTOGENETICS (2021)

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Review Oncology

Targeting BCL-2 in Cancer: Advances, Challenges, and Perspectives

Shirin Hafezi et al.

Summary: Apoptosis is the main form of cell death regulated by the BCL-2 family of proteins. Overexpression of antiapoptotic proteins in malignant cells offers survival advantages but also presents opportunities for targeted therapies. Studies targeting BCL-2 proteins, including the development of venetoclax, show promise for effective treatment in cancer.

CANCERS (2021)

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Article Oncology

Wilms Tumor 1 Mutations Are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia

Yin Wang et al.

Summary: WT1 mutations are associated with poor prognosis in pediatric AML, especially when co-occurring with FLT3/ITD mutations. Hematopoietic stem cell transplantation may improve the prognosis of patients with WT1 mutations.

FRONTIERS IN ONCOLOGY (2021)

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Article Biochemistry & Molecular Biology

Optimizing DNA hypomethylating therapy in acute myeloid leukemia and myelodysplastic syndromes

Jasmin Straube et al.

Summary: DNA hypomethylating agents AZA and DAC have shown potential in improving survival in MDS and AML patients, particularly in older patients and in combination with novel agents. An oral formulation of AZA has shown advantages in AML patients, while DAC and AZA have been found to significantly improve survival in elderly AML patients through combination with other drugs.

BIOESSAYS (2021)

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Article Hematology

Targeting intracellular WT1 in AML with a novel RMF-peptide-MHC-specific T-cell bispecific antibody

Christian Augsberger et al.

Summary: The novel T-cell bispecific (TCB) antibody targets intracellular antigens, recognizing multiple leukemia-associated targets. WT1-TCB demonstrates potent killing of AML cells through various methods, with enhanced cytotoxicity when combined with immunomodulatory drugs.

BLOOD (2021)

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Article Medical Laboratory Technology

Molecular Genetics of Pediatric Acute Myeloid Leukemia

Bryan Krock et al.

CLINICS IN LABORATORY MEDICINE (2021)

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Article Oncology

Gemtuzumab Ozogamicin Improves Event-Free Survival and Reduces Relapse in Pediatric KMT2A-Rearranged AML: Results From the Phase III Children's Oncology Group Trial AAML0531

Jessica A. Pollard et al.

Summary: Using the CD33-targeted agent gemtuzumab ozogamicin (GO) improved event-free survival (EFS) and reduced relapse risk (RR) for pediatric patients with KMT2A-rearranged acute myeloid leukemia (AML). Incorporating GO into treatment may lead to better outcomes, especially when combined with hematopoietic stem cell transplant (HSCT).

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Review Cell & Tissue Engineering

Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients

Faroogh Marofi et al.

Summary: AML is a life-threatening disease with low survival rates, but CAR T cell therapy shows promising results as a novel treatment method, especially in the treatment of hematological cancers. Gradual advancements in targeting AML antigens with CAR T cell therapy have led to more effective and specific therapies with impressive clinical outcomes.

STEM CELL RESEARCH & THERAPY (2021)

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Review Genetics & Heredity

Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge

Julie Quessada et al.

Summary: Pediatric acute myeloid leukemia is a rare and heterogeneous disease with improved treatment outcomes but high relapse rates. Cytogenetics play a crucial role in diagnosis and prognosis, with cytogenetic abnormalities in current therapeutic protocols guiding risk-adapted therapy.

GENES (2021)

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Review Medicine, General & Internal

Antibody-Drug Conjugates for the Treatment of Acute Pediatric Leukemia

Jamie L. Stokke et al.

Summary: ADCs have emerged as a promising therapeutic approach for leukemia, particularly in pediatric acute leukemias, by utilizing monoclonal antibodies linked to cytotoxic payloads. Targeting CD22 has shown significant efficacy in B-ALL, with ongoing efforts to identify more leukemia-specific targets and enhance ADC structure for improved therapeutic outcomes.

JOURNAL OF CLINICAL MEDICINE (2021)

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Article Oncology

Advances in the First Line Treatment of Pediatric Acute Myeloid Leukemia in the Polish Pediatric Leukemia and Lymphoma Study Group from 1983 to 2019

Malgorzata Czogala et al.

Summary: Poland has made significant progress in treating pediatric acute myeloid leukemia since 1983, with improved survival rates attributed to standardized treatment protocols and consideration of genetic prognostic factors.

CANCERS (2021)

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Article Oncology

FLT3 mutated acute myeloid leukemia: 2021 treatment algorithm

Naval Daver et al.

Summary: Approximately 30% of newly diagnosed AML patients have FLT3 gene mutations, with FLT3-ITDmut showing adverse prognostic impact. Guidelines recommend rapid molecular testing for FLT3(mut) and early use of targeted agents, but challenges remain in prolonged remission, limited options for refractory patients, and resistance mechanisms that call for multi-agent therapies.

BLOOD CANCER JOURNAL (2021)

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Review Oncology

FLT3 mutations in acute myeloid leukemia: Therapeutic paradigm beyond inhibitor development

Hitoshi Kiyoi et al.

CANCER SCIENCE (2020)

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Review Pediatrics

Pediatric acute myeloid leukemia: updates on biology, risk stratification, and therapy

Caitlin W. Elgarten et al.

CURRENT OPINION IN PEDIATRICS (2020)

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Article Hematology

Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Group

Richard Aplenc et al.

HAEMATOLOGICA (2020)

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Article Oncology

Causes of early death and treatment-related death in newly diagnosed pediatric acute myeloid leukemia: Recent experiences of the Dutch Childhood Oncology Group

Kim Klein et al.

PEDIATRIC BLOOD & CANCER (2020)

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Article Hematology

Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial

Andrew H. Wei et al.

BLOOD (2020)

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Article Oncology

Venetoclax is safe and efficacious in relapsed/refractory AML

Chezi Ganzel et al.

LEUKEMIA & LYMPHOMA (2020)

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Article Biotechnology & Applied Microbiology

Targeting CD33 in Chemoresistant AML Patient-Derived Xenografts by CAR-CIK Cells Modified with an Improved SB Transposon System

Maria Caterina Rotiroti et al.

MOLECULAR THERAPY (2020)

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Article Oncology

Successful Anti-CLL1 CAR T-Cell Therapy in Secondary Acute Myeloid Leukemia

Hui Zhang et al.

FRONTIERS IN ONCOLOGY (2020)

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Article Oncology

Camidanlumab tesirine, an antibody-drug conjugate, in relapsed/refractory CD25-positive acute myeloid leukemia or acute lymphoblastic leukemia: A phase I study

Aaron D. Goldberg et al.

LEUKEMIA RESEARCH (2020)

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Article Oncology

Characterization of a Novel FLT3 BITE Molecule for the Treatment of Acute Myeloid Leukemia

Bettina Brauchle et al.

MOLECULAR CANCER THERAPEUTICS (2020)

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Article Oncology

Safety, pharmacokinetics, and pharmacodynamics of panobinostat in children, adolescents, and young adults with relapsed acute myeloid leukemia

Seth E. Karol et al.

CANCER (2020)

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Article Oncology

Single-center pediatric experience with venetoclax and azacitidine as treatment for myelodysplastic syndrome and acute myeloid leukemia

Amanda C. Winters et al.

PEDIATRIC BLOOD & CANCER (2020)

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Review Biochemistry & Molecular Biology

Antibody-Drug Conjugates for Cancer Therapy

Umbreen Hafeez et al.

MOLECULES (2020)

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Article Oncology

Modulating TNFα activity allows transgenic IL15-Expressing CLL-1 CAR T cells to safely eliminate acute myeloid leukemia

Pinar Ataca Atilla et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2020)

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Article Hematology

Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial

Maria Teresa Voso et al.

BLOOD ADVANCES (2020)

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Article Medicine, General & Internal

Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission

A. H. Wei et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Review Pharmacology & Pharmacy

Novel therapies for AML: a round-up for clinicians

Mahesh Swaminathan et al.

EXPERT REVIEW OF CLINICAL PHARMACOLOGY (2020)

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Article Immunology

Chimeric Antigen Receptor T Cells Targeting NKG2D-Ligands Show Robust Efficacy Against Acute Myeloid Leukemia and T-Cell Acute Lymphoblastic Leukemia

Lina Driouk et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Meeting Abstract Hematology

Improved Outcome in Pediatric AML - the AML-BFM 2012 Study

Katharina Waack et al.

BLOOD (2020)

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Review Cell Biology

Targeting BCL-2 in B-cell malignancies and overcoming therapeutic resistance

Isha Kapoor et al.

CELL DEATH & DISEASE (2020)

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Review Pediatrics

Harnessing T Cells to Target Pediatric Acute Myeloid Leukemia: CARs, BiTEs, and Beyond

Rebecca Epperly et al.

CHILDREN-BASEL (2020)

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Article Oncology

An Anti-CLL-1 Antibody-Drug Conjugate for the Treatment of Acute Myeloid Leukemia

Bing Zheng et al.

CLINICAL CANCER RESEARCH (2019)

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Letter Hematology

A phase 1/2, open-label, dose-escalation study of midostaurin in children with relapsed or refractory acute leukaemia

C. Michel Zwaan et al.

BRITISH JOURNAL OF HAEMATOLOGY (2019)

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Article Hematology

Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial

Juliette Lambert et al.

HAEMATOLOGICA (2019)

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Article Oncology

Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study

Andrew H. Wei et al.

JOURNAL OF CLINICAL ONCOLOGY (2019)

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Article Oncology

Clofarabine Can Replace Anthracyclines and Etoposide in Remission Induction Therapy for Childhood Acute Myeloid Leukemia: The AML08 Multicenter, Randomized Phase III Trial

Jeffrey E. Rubnitz et al.

JOURNAL OF CLINICAL ONCOLOGY (2019)

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Article Oncology

Development of a novel fully-human anti-CD123 antibody to target acute myeloid leukemia

Cornelia Hutmacher et al.

LEUKEMIA RESEARCH (2019)

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Article Oncology

Safety and efficacy of oral panobinostat plus chemotherapy in patients aged 65 years or younger with high-risk acute myeloid leukemia

Daniel J. DeAngelo et al.

LEUKEMIA RESEARCH (2019)

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Review Pediatrics

Targeted Therapies for Pediatric AML: Gaps and Perspective

Annalisa Lonetti et al.

FRONTIERS IN PEDIATRICS (2019)

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Review Oncology

HDAC Inhibitors in Acute Myeloid Leukemia

Edurne San Jose-Eneriz et al.

CANCERS (2019)

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Article Oncology

Phase I Trial of Autologous CAR T Cells Targeting NKG2D Ligands in Patients with AML/MDS and Multiple Myeloma

Susanne H. Baumeister et al.

CANCER IMMUNOLOGY RESEARCH (2019)

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Article Hematology

Pracinostat plus azacitidine in older patients with newly diagnosed acute myeloid leukemia: results of a phase 2 study

Guillermo Garcia-Manero et al.

BLOOD ADVANCES (2019)

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Article Oncology

Accelerating drug development in pediatric cancer: a novel Phase I study design of venetoclax in relapsed/refractory malignancies

Andrew E. Place et al.

FUTURE ONCOLOGY (2018)

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Review Oncology

Addition of histone deacetylase inhibitors does not improve prognosis in patients with myelodysplastic syndrome and acute myeloid leukemia compared with hypomethylating agents alone: A systematic review and meta-analysis of seven prospective cohort studies

Tingting Pan et al.

LEUKEMIA RESEARCH (2018)

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Review Biochemistry & Molecular Biology

Epigenetic Modifiers in Myeloid Malignancies: The Role of Histone Deacetylase Inhibitors

Johanna S. Ungerstedt

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2018)

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Article Multidisciplinary Sciences

Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias

Shahzya Chaudhury et al.

NATURE COMMUNICATIONS (2018)

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Article Oncology

CD33/CD3-bispecific T-cell engaging (BiTE®) antibody construct targets monocytic AML myeloid-derived suppressor cells

Regina Jitschin et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2018)

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Article Hematology

A CD123-targeting antibody-drug conjugate, IMGN632, designed to eradicate AML while sparing normal bone marrow cells

Yelena Kovtun et al.

BLOOD ADVANCES (2018)

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Article Medicine, General & Internal

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

R. M. Stone et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

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Article Oncology

Gemtuzumab Ozogamicin in Children and Adolescents With De Novo Acute Myeloid Leukemia Improves Event-Free Survival by Reducing Relapse Risk: Results From the Randomized Phase III Children's Oncology Group Trial AAML0531

Alan S. Gamis et al.

JOURNAL OF CLINICAL ONCOLOGY (2014)

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Review Oncology

The Basic Principles of Chimeric Antigen Receptor Design

Michel Sadelain et al.

CANCER DISCOVERY (2013)

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Review Hematology

Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel

Ursula Creutzig et al.

BLOOD (2012)

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Article Oncology

DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia

Maria E. Figueroa et al.

CANCER CELL (2010)

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Article Oncology

Attempts to Optimize Induction and Consolidation Treatment in Acute Myeloid Leukemia: Results of the MRC AML12 Trial

Alan K. Burnett et al.

JOURNAL OF CLINICAL ONCOLOGY (2010)

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Article Oncology

Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial

Jeffrey E. Rubnitz et al.

LANCET ONCOLOGY (2010)

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Article Oncology

Combination of cladribine and cytarabine is effective for childhood acute myeloid leukemia: results of the St Jude AML97 trial

J. E. Rubnitz et al.

LEUKEMIA (2009)

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Article Hematology

Outcomes in CCG-2961, a Children's Oncology Group Phase 3 Trial for untreated pediatric acute myeloid leukemia: a report from the Children's Oncology Group

Beverly J. Lange et al.

BLOOD (2008)

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Article Hematology

Results of consecutive trials for children newly diagnosed with acute myeloid leukemia from the Australian and New Zealand Children's Cancer Study Group

TA O'Brien et al.

BLOOD (2002)

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Article Oncology

Idarubicin improves blast cell clearance during induction therapy in children with AML:: results of study AML-BFM 93

U Creutzig et al.

LEUKEMIA (2001)

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