Advances in integrated translatomics and proteomics techniques have successfully identified the hidden layer of the microproteome that has historically been regarded as non-coding. Investigations into the involvement of microproteins in hematological malignancies may help address the key gaps that persist despite extensive genomic and transcriptomic profiling. Many blood cancers display extensive clonal heterogeneity, dynamic evolution, and limited actionable mutations. Consequently, mutation-centric approaches are insufficient to fully elucidate disease behavior and identify novel treatment methods. Understanding the role of microproteins may help clarify the relationship between aberrant non-coding RNA expression and observed phenotypes in malignant cells, by finding the direct key contributors to signaling, metabolic rewiring, and epigenetic regulation. These tiny molecules may uncover an unexplored reservoir of disease regulators and potential antigenic targets for immunotherapy. Antigenic microproteins, arising from unconventional coding regions such as ncRNA transcripts, may elicit T-cell responses and represent a previously unrecognized class of immunogenic molecules with therapeutic relevance. This review highlights the need for exploration of the role of microproteins in pathobiology of hematological malignancies and provides a framework to support future studies evaluating the immunogenic potential of microproteins as antigenic targets.
Hereditary hemolytic anemia (HHA) is a group of inherited disorders characterized by a shortened red blood cell (RBC) lifespan due to intrinsic defects involving the RBC membrane, cytoskeleton, hemoglobin, or metabolic enzymes. Traditionally, membranopathies have been the most common type of HHA in Korea, whereas hemoglobinopathies have been rare. The epidemiology of HHA has recently changed in Korea because of changes in population dynamics owing to an increase in international marriages and immigration. Accurate diagnosis is essential for appropriate management because therapeutic responses differ among HHA subtypes. The initial evaluation begins with the confirmation of hemolysis and exclusion of immune-mediated or microangiopathic processes. The diagnostic process integrates RBC indices, reticulocyte responses, and peripheral blood smears (PBS), supplemented by specialized assays. The eosin-5-maleimide binding test and osmotic fragility tests are valuable for detecting hereditary spherocytosis (HS), whereas osmotic gradient ektacytometry and membrane protein analysis provide comprehensive assessments of membranopathies. PBS can provide initial insights into hemoglobinopathies. Enzymopathies usually result in nonspecific normocytic hemolytic anemia, and sequential enzyme activity and genetic testing are recommended. When phenotypic evaluation is limited, multigene sequencing panels allow for the precise identification of pathogenic variants, substantially improving diagnostic accuracy. Management strategies depend on the patient’s specific diagnosis. Although splenectomy is effective for various HHA types, such as HS, pyruvate kinase deficiency, thalassemia, and selected cases of hereditary elliptocytosis, it provides little benefit and carries a significant risk in patients with hereditary stomatocytosis, hereditary xerocytosis, and congenital dyserythropoietic anemia type I. Therefore, accurate diagnosis before making a surgical decision is crucial. As genetic insights refine diagnostic pathways and targeted therapies such as pyruvate kinase activators emerge, individualized management strategies remain central to optimizing outcomes in patients with HHA.
CHASE (cyclophosphamide, high-dose cytarabine, dexamethasone, and etoposide) is an anthracycline- and platinum-free salvage regimen. This study evaluated the real-world efficacy and safety of CHASE in relapsed or refractory non-Hodgkin lymphoma (NHL), focusing on its role as salvage or bridging therapy before transplantation and cellular therapy (TCT). We retrospectively analyzed 53 patients with relapsed or refractory NHL who received CHASE at Jichi Medical University Hospital between 2014 and 2026. Double-refractory (DR) disease was defined as refractoriness to both anthracycline- and platinum-based regimens. Progression-free survival (PFS), overall survival (OS), response, TCT completion, and adverse events were assessed. The overall response and complete response rates were 47.2
Chronic lymphocytic leukemia (CLL) management has evolved into a precision-medicine paradigm, with genetic risk factors such as TP53 and IGHV status serving as key determinants of frontline treatment selection. The therapeutic landscape has expanded to include fixed-duration options alongside established continuous regimens. This expansion has enabled personalized management strategies incorporating measurable residual disease-guided treatment approaches aimed at achieving deeper responses while minimizing long-term toxicity and resistance. In a relapsed/refractory setting, treatment selection must be guided by prior treatment exposure, identified molecular mechanisms of resistance, and the availability of novel agents. In this review, we have synthesized the latest clinical evidence and international guidelines to provide an updated, evidence-based algorithm for the diagnosis and management of CLL. Furthermore, we examined the clinical efficacy reported in pivotal trials involving patients with relapsed/refractory CLL and discuss the potential of next-generation therapies, including non-covalent Bruton tyrosine kinase (BTK) inhibitors, BTK degraders, and cellular immunotherapies, to expand treatment options for high-risk patients. Finally, we addressed the clinical challenges of Richter’s transformation, emphasizing the importance of clonality assessment and the urgent need for further clinical trials and innovative therapeutic approaches to improve long-term outcomes in this patient population.
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated hemolysis. Although C5 inhibitors effectively control intravascular hemolysis, some patients develop clinically significant extravascular hemolysis (EVH) because of upstream C3 deposition. A 56-year-old woman was diagnosed with PNH in 2019 and managed with intermittent transfusions. In October 2024, she developed progressive renal dysfunction; the PNH clone size was 95.72
