[caption id="attachment_73594" align="aligncenter" width="500"] Photo by Christina Victoria Craft on Unsplash[/caption]
Treatment options for hematologic malignancies have evolved considerably over the past decade. Bruton's tyrosine kinase (BTK) inhibitors are an important class of targeted agents that have been introduced into clinical practice for the management of select blood cancers, with multiple clinical studies evaluating their impact on disease outcomes.
These therapies work by targeting a specific enzyme involved in B-cell signaling — a pathway that is dysregulated in several B-cell malignancies — and have received regulatory approval for use in a number of hematologic conditions.
Photo by Christina Victoria Craft on Unsplash[/caption]
Treatment options for hematologic malignancies have evolved considerably over the past decade. Bruton's tyrosine kinase (BTK) inhibitors are an important class of targeted agents that have been introduced into clinical practice for the management of select blood cancers, with multiple clinical studies evaluating their impact on disease outcomes.
These therapies work by targeting a specific enzyme involved in B-cell signaling — a pathway that is dysregulated in several B-cell malignancies — and have received regulatory approval for use in a number of hematologic conditions.
Dr. Yu Mengge[/caption]
Dr Yu Mengge
Research Fellow, Cancer & Stem Cell Biology Signature Research Programme
Duke-NUS Medical School
MedicalResearch.com: What is the background for this study?
Response: The background of this study is rooted in the observation that certain genetic variations among East Asian populations, notably the BIM deletion polymorphism (BDP), impact treatment outcomes in chronic myeloid leukaemia (CML).
Patients with the BDP show resistance to conventional treatments, specifically tyrosine kinase inhibitors like imatinib. This resistance stems from the variant's role in promoting cancer cell survival, which leads to more aggressive disease progression.
Bone marrow aspiration is a medical procedure where a small amount of the liquid part of your bone marrow is removed for examination. A 
Dr. Thomas[/caption]
Dr. Daniel Thomas MD PhD FRACP FRCPA
Program Leader, Blood Cancer
Precision Medicine Theme at the South Australia Health Medical Research Institute
Clinical Hematologist, Royal Adelaide Hospital
Associate Professor, Adelaide Medical School, The University of Adelaide
MedicalResearch.com: What is the background for this study? Would you briefly describe the condition of CMML?
Response: Chronic myelomonocytic leukemia (CMML) is a rare, but increasingly frequent, clonal stem cell disorder that results in hyperproliferation of inflammatory monocytes, a form of white blood cells. It features both myelodysplasia and myeloproliferation. CMML is most often found in older adults and leads to anemia, decreased quality of life, and an increased risk of acute myeloid leukemia (AML).
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that stimulates production, growth, differentiation, activation, and function of myeloid cells (monocytes, neutrophils, and eosinophils). In the presence of RAS-pathway mutations, a greater sensitivity to GM-CSF contributes to the hyperproliferation of myelocytes in myelodysplastic leukemias such as CMML, juvenile myelomonocytic leukemia (JMML), and acute myeloid leukemia (AML). In CMML, greater sensitivity to GM-CSF stimulates excessive monocytic precursor proliferation.
The PREACH-M Trial, which stands for PREcision Approach to CHronic Myelomonocytic Leukemia, assesses the efficacy of lenzilumab in addition to azacitidine in treatment-naïve CMML participants with RAS-pathway mutations (KRAS, NRAS, CBL) and separately high dose ascorbate in participants with TET2 mutations who do not have RAS-pathway mutations. The study is currently underway and actively enrolling. It is being conducted and funded by the South Australian Health and Medical Research Institute (SAHMRI).