Novel RNAs Insights Toward AML Development

Oct 7, 2021 11:00:00 AM / by Champions Oncology posted in Hematological Malignancies


Somatic mutations in the additional sex comb-like 1 (ASXL1) gene have been identified in multiple hematologic malignancies, including acute myeloid leukemia (AML), and are associated with poor prognoses1. ASXL1 encodes a nuclear protein that regulates epigenetic remodeling and transcription through interactions with polycomb complex proteins and transcriptional activators and repressors. Several ASXL1 mutations have been associated with loss of protein expression that leads to myeloid transformation2. In contrast, gain-of-function mutations in ASXL1 result in expression of a truncated ASXL1 protein that can bind to BRCA-1 associated protein 1 (BAP1) and cause leukemogenesis3,4. Targeted reduction of BAP1 activity is sufficient to prevent this malignancy process5.

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Regulatory T Cells in CLL: Immune System Exhaustion and Potential Restoration, and the Role of Immuno-Oncology Therapies

Sep 2, 2021 1:00:00 PM / by Champions Oncology posted in Immuno-Oncology, Hematological Malignancies

Chronic lymphocytic leukemia (CLL) is one of the most commonly occurring hematologic malignances with no known cure and is defined by the clonal expansion and accumulation of CD5+ B cells in the blood and bone marrow. Standard treatments to manage disease include chemotherapy and rituximab (anti-CD20 monoclonal antibody). Newer therapies that are less prone to resistance or treatment failure are currently being examined, such as Bruton tyrosine kinase (BTK) inhibitors and anti-CD20 biosimilars[1],[2].

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Triplet Therapy for Genetic Subtypes of AML

Jun 30, 2021 1:00:00 PM / by Champions Oncology posted in Hematological Malignancies

Acute myeloid leukemia (AML) is one of the most frequently occurring types of leukemia and can have widely varying treatment outcomes. Multiple mutations and cytogenetic abnormalities have been characterized in AML, and recent studies have been essential to defining specific mutations that confer resistance to standard chemotherapies or molecular inhibitors. A mutation in the tyrosine kinase domain of FMS-like tyrosine kinase 3 (FLT3) has been associated with resistance to FLT3 inhibitors[1], and molecular diagnostics are critical to identifying mutations that lead to treatment failure.

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A Needle in a Haystack – Finding Rare AML Cell Populations by Flow Cytometry

Jun 10, 2021 11:00:00 AM / by Champions Oncology posted in Hematological Malignancies, Preclinical Flow Cytometry

Hematologic malignancies include a wide array of lymphomas and leukemias that affect different immune cell subsets. Acute myelogenous leukemia (AML) is one of the most commonly occurring leukemias in adults and children. AML is a highly heterogenous disease that can be caused by spontaneous gene mutations or chromosomal translocations, which results in the proliferation of dysfunctional myeloid cells. Cytogenetic and morphologic analyses have been the gold standard methods used in AML diagnosis, but flow cytometry-based protocols are becoming more widely used and validated as complementary diagnostic methods that can be coupled with these analyses to better guide treatment plans. Flow cytometry has also become an essential tool to understand AML progression and develop and evaluate novel therapeutics.

Consider these aspects of flow cytometry-based analysis of AML for exploratory or preclinical research.

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Stem Cell Transplantation in CLL: Almost Gone but Not Forgotten

Jun 3, 2021 11:00:00 AM / by Champions Oncology posted in Hematological Malignancies

Advances in molecular diagnostics and ex vivo drug sensitivity screening have greatly improved the use of targeted therapies for the treatment of chronic lymphocytic leukemia (CLL), such as B cell receptor signaling inhibitors, which include the Bruton tyrosine kinase (BTK) inhibitors like ibrutinib[1] and acalabrutinib and the phosphoinositide 3-kinase (PI3K) inhibitors duvelisib and idelalisib[2], as well as the BCL2 inhibitor venetoclax[3]. For most patients that are matched appropriately with these treatments, they show greatly improved progression-free survival and overall survival.

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Culture Clash: Autologous versus Allogeneic Cells in Oncology

May 6, 2021 11:00:00 AM / by Champions Oncology posted in Hematological Malignancies, Ex Vivo Platforms

Adoptive cell therapies (ACTs) are being broadly tested and implemented in the treatment of a wide range of cancers, but the success of these therapies has been limited by the challenges of expanding cells of interest ex vivo. Most studies collect peripheral blood cells from a patient and expand, enrich or modify tumor-specific cells in a laboratory environment to create a blood product with tumor-targeting cells that can be reinfused into the patient. If the blood product is re-infused into the same patient, it is considered an autologous transplant, but if the cells originate from a different donor, it is considered an allogeneic transplant.

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Now that's a SMARTrial: Ex Vivo Drug Screening in CLL as a Biomarker for Clinical Outcomes

Apr 29, 2021 1:00:00 PM / by Champions Oncology posted in Hematological Malignancies

The current landscape for immunotherapy treatment of blood cancers has been advanced by breakthroughs in molecular diagnostics and personalized medicine. Now patients not only know the type of hematologic malignancy they have, but they may also be aware of unique mutations or variations associated with their cancer that can instruct treatment choices.

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Overcoming Drug Resistance in AML: Targeting Tricky Signaling Pathways

Apr 8, 2021 11:00:00 AM / by Champions Oncology posted in Hematological Malignancies

Resistance to anti-cancer treatments is a significant therapeutic challenge and is typically associated with mutations in signaling pathways that are involved in cell proliferation, survival, and tumorigenesis. Genomic analyses of relapsed pediatric acute myeloid leukemia (AML) patients have identified mutations, deletions, and changes in promoter methylation associated with Wnt-β-catenin signaling[1],[2]. Mutations in the PI3K-Akt pathway are also frequently associated with treatment resistance in AML and many other cancers[3],[4]. Hematopoietic stem cells are particularly sensitive to mutations in these signaling pathways and numerous studies have shown that targeting each of these pathways separately is associated with poor efficacy and emergence of resistance[5]. AML resistance not only emerges from chemotherapy but can also be seen in response to immunotherapy[6].

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Novel RNAs Insights Toward AML Development

Mar 4, 2021 10:45:00 AM / by Champions Oncology posted in Hematological Malignancies


Somatic mutations in the additional sex comb-like 1 (ASXL1) gene have been identified in multiple hematologic malignancies, including acute myeloid leukemia (AML), and are associated with poor prognoses1. ASXL1 encodes a nuclear protein that regulates epigenetic remodeling and transcription through interactions with polycomb complex proteins and transcriptional activators and repressors. Several ASXL1 mutations have been associated with loss of protein expression that leads to myeloid transformation2. In contrast, gain-of-function mutations in ASXL1 result in expression of a truncated ASXL1 protein that can bind to BRCA-1 associated protein 1 (BAP1) and cause leukemogenesis3,4. Targeted reduction of BAP1 activity is sufficient to prevent this malignancy process5.

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Understanding PD-1/PD-L1 for Ex Vivo Drug Screening for AML

Feb 11, 2021 10:45:00 AM / by Champions Oncology posted in Hematological Malignancies

Acute myeloid leukemia (AML) is an aggressive hematological malignancy that has been treated in the same way for the last several decades and typically includes standard chemotherapy protocols as well as bone marrow (BM) transplantation.  Despite advances in the field of immunotherapy, AML has been challenging to treat with immune checkpoint inhibitors that target Programmed Death (PD) - 1/PD-Ligand (L) 1 inhibitors.

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