Idiopathic multicentric Castleman disease (iMCD) is a rare hematological disease of heterogenous presentation, with symptoms ranging from mild to severe and life-threatening. A severe subtype of iMCD is characterized by thrombocytopenia, anasarca (including pleural effusion and ascites), fever, reticulin myelofibrosis or renal dysfunction, and organomegaly (iMCD-TAFRO). Early identification and treatment of iMCD-TAFRO is crucial because of its rapid onset, severe renal dysfunction and high mortality risk. However, diagnosing iMCD-TAFRO can be difficult due to a lack of diagnostic biomarkers and symptoms that overlap with a variety of lymphoproliferative, infectious, and rheumatological diseases. Although the exact etiology of iMCD-TAFRO is unknown, interleukin (IL)-6 has been identified as a critical pathological driver, and the IL-6 antagonist siltuximab is recommended as first-line treatment. While many patients with iMCD-TAFRO have abnormal kidney function and will require nephrology care, evidence describing kidney histopathology and kidney involvement in this condition is limited. Herein, we review the disease state and recent advances with a focus on renal histopathology and the mechanisms of kidney injury in iMCD-TAFRO. We also present and discuss a case report of a patient with iMCD-TAFRO and acute kidney failure. Our aim is to draw attention to the spectrum of kidney involvement in iMCD-TAFRO, as well as raise awareness to the importance of early recognition and appropriate treatment of this rare condition.

As part of its initiative to harmonize practices in allogeneic hematopoietic stem cell transplantation, the SFGM-TC devoted a workshop to the management of myelofibrosis. Discussions focused on patient selection, peri-transplant management of ruxolitinib, and the choice of conditioning regimen and donor. The workshop emphasized the need for an individualized approach integrating clinical and molecular prognostic scores, assessment of transplant-related risk, and treatment response. Several questions remain open, particularly regarding the role of dynamic molecular monitoring and optimal peri-transplant ruxolitinib management.

Lysozyme-associated nephropathy (LyN) is an underrecognized cause of kidney dysfunction, commonly associated with chronic myelomonocytic leukemia (CMML). We present two cases of LyN with distinct clinical manifestations. In Case 1, an 80-year-old man with primary myelofibrosis developed progressive monocytosis, kidney dysfunction, proteinuria, and elevated serum and urinary lysozyme levels. Kidney biopsy revealed lysozyme-positive intracytoplasmic granules within proximal tubular cells, confirming the diagnosis of LyN. Notably, the progressive increase in the number of lysozyme- positive bone marrow cells may serve as an indicator of LyN activity. Treatment with hydroxycarbamide, a cytoreductive agent, and ruxolitinib, a Janus kinase inhibitor, successfully stabilized kidney function. In Case 2, a 63-year-old man with CMML developed acute kidney injury. Although the etiology of kidney dysfunction could not be determined during life, autopsy revealed diagnostic features of LyN. To further investigate LyN pathophysiology, we performed the first mass spectrometry-based proteomic analysis of proximal tubules in two cases. LyN samples showed marked lysozyme accumulation and upregulation of proteins involved in lysosomal system, lipid metabolism, cellular stress, and chronic inflammation. These findings suggest that chronic lysozyme overload disrupts intracellular homeostasis and contributes to kidney injury. LyN is underdiagnosed as unexplained tubular damage or chronic kidney disease, highlighting the need for awareness of the clinicopathological features.

Fas-associated phosphatase-1 (FAP-1), a nonreceptor protein tyrosine phosphatase, has been implicated in multiple signaling pathways, but its in vivo role remains unclear. Here, we show that FAP-1-deficient (FAP-1ΔP/ΔP) mice develop early megakaryocyte hyperplasia with defective platelet function and occasional hemorrhagic manifestations, accompanied by myelofibrosis-like features in aged animals. Bone marrow analysis revealed impaired demarcation membrane system (DMS) development with pre-DMS arrest in megakaryocytes, leading to defective proplatelet formation and impaired platelet function, with prolonged bleeding partly associated with reduced clot retraction. Mechanistically, FAP-1 deficiency induces sustained Src activation and cofilin inactivation, impairing perinuclear actin remodeling required for DMS expansion and resulting in pre-DMS arrest. With aging, approximately half of mice develop a symptomatic phenotype characterized by extramedullary hematopoiesis, hepatosplenomegaly, anemia, and thrombocytopenia; among these, most remain in a prefibrotic state, while a subset progresses to fibrosis-like changes. Bone marrow transplantation demonstrates that megakaryocyte abnormalities and fibrosis-associated changes are hematopoietic cell-intrinsic and partially transferable. Pharmacologic inhibition of Src with dasatinib attenuates these defects in FAP-1-deficient mice, supporting pathway specificity. In patients with primary myelofibrosis, reduced FAP-1 expression is associated with pre-DMS megakaryocyte accumulation, abnormal DMS and actin organization, and Src activation, supporting clinical relevance. Collectively, we identify a FAP-1-dependent mechanism governing Src-cofilin-mediated actin remodeling required for megakaryocyte maturation and platelet function, and suggest this pathway as a potential therapeutic target for platelet dysfunction, hemorrhagic complications, and fibrosis-associated disease.

Leukemia relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the leading death cause, with extramedullary disease history as an independent relapse risk factor in acute leukemia. We analyzed 10 patients with extramedullary disease history who received allo-HSCT with mitoxantrone liposome (Lipo-MIT)-containing conditioning at our center (Dec 2022-Jan 2025). Median age was 39.5 (14-63), 7 had acute myeloid leukemia (AML, including myeloid sarcoma), 2 T lymphoblastic lymphoma/leukemia, and 1 B-cell acute lymphoblastic leukemia. Pre-transplant, 4 were in complete remission (CR) (1 with minimal residual disease [MRD] positivity) and 6 had residual lesions (2 with BM blasts ≥ 5%, 2 with MRD positivity). The conditioning regimen was Lipo-MIT + total body irradiation/busulfan + cyclophosphamide ± cytarabine, with a median Lipo-MIT dose of 26.1 (18.5-28.9) mg/m2. Mucosal injury showed a high incidence (9/10) after conditioning, but most were transient and controllable with supportive care. Engraftment succeeded in 9 patients, with a median neutrophil recovery time of 16 (11-21) days and platelet recovery time of 20 (11-39) days. Only 1 patient developed grade 2 skin acute graft-versus-host disease (aGVHD). All 9 engrafted patients achieved complete remission (CR) post-transplantation; one had MRD positivity at + 177 days, which turned negative after chemotherapy combined with donor lymphocyte infusion. One patient relapsed at + 234 days and died at + 272 days. The patient with engraftment failure died at + 346 days due to disease progression, with a history of polycythemia vera complicated by myelofibrosis. Lipo-MIT conditioning shows promising efficacy/safety for allo-HSCT in extramedullary disease patients. Randomized trials are needed.

Classic BCR::ABL1-negative myeloproliferative neoplasms (MPNs)-polycythaemia vera, essential thrombocythaemia, and primary myelofibrosis-are clonal haematopoietic stem cell disorders with marked heterogeneity in clinical phenotype, disease trajectory, and therapeutic response. Genomic stratification by driver and cooperating mutations only partially accounts for this variability, leaving gaps in predicting thrombotic risk, fibrotic progression, leukaemic transformation, and treatment benefit. Proteomics bridges this gap by providing function-proximal readouts of protein abundance, post-translational modifications, pathway activity, and intercellular signalling that genomics and transcriptomics cannot capture, positioning it as a theranostic platform in which the same molecular readouts simultaneously inform diagnostic stratification and therapeutic decision-making. We propose a five-stage translational framework spanning from discovery-scale mass spectrometry and affinity-based plasma profiling to targeted validation, multicentre standardisation, and machine learning-integrated clinical panels. Proteomic evidence is synthesised across the following four disease axes: clonal fitness in haematopoietic stem and progenitor cells; bone marrow microenvironmental remodelling and fibrosis; chronic inflammation and thrombosis; and leukaemic transformation. We further describe how phosphoproteomics reveals resistance mechanisms to JAK inhibitors, including AXL-MAPK bypass and PP2A-autophagy-mediated tolerance, and how protein-level biomarkers (BCL2-BCL-XL, RAS-ERK, CAMK2G, and ROCK1/2) can guide individualised therapeutic selection. Affinity-based platforms (Olink PEA and SomaScan) and spatially resolved technologies (CODEX and single-cell proteomics) complement discovery proteomics. At present, however, this evidence base is constrained by small and heterogeneous cohorts, limited cross-platform reproducibility, and a scarcity of independent external validation for candidate protein panels. Realising this vision will require multicentre standardisation, analytically validated panel assays, and prospective clinical studies that translate molecular findings into decision-grade tools for patients with MPNs.

Adenoid cystic carcinoma (ACC) is a slow-growing malignancy characterised by late recurrence, making long-term follow-up essential. We report a case of 55-year-old woman who presented with exudative right pleural effusion and subcarinal lymphadenopathy after haematopoietic stem cell transplantation for myelofibrosis. She had undergone surgery and radiotherapy for primary tracheal ACC 24 years prior. Although haematologic disease-related conditions were initially suspected, endobronchial ultrasound-guided transbronchial needle aspiration of the subcarinal lymph node revealed isolated recurrence of ACC, with no evidence of pleural malignancy on pleural biopsy results. Because ACC progresses more slowly than many other malignancies, the growth rate alone does not reliably distinguish benign from malignant lesions. Therefore, a history of ACC should always be considered, and a tissue diagnosis should be pursued when clinically indicated.

Primary myelofibrosis (PMF) is the clonal proliferation of common myeloid progenitor (CMP) cells and can transform into acute myeloid leukemia (AML). The exact transformation process and cell lines involved are not well-understood. A patient with PMF received an allogenic hematopoietic stem cell transplant (alloHCT) from his major ABO incompatible sibling and developed pure red cell aplasia that resolved when his blood type switched to that of his donor's. He relapsed with AML 10 months after alloHCT; interestingly, his blood type remained his donor's type. This supports that AML in this patient with PMF stemmed from more committed progenitors (myeloblasts) than CMP.

Background/Objectives: Chronic myeloid leukemia (CML), essential thrombocythemia (ET), primary myelofibrosis (PMF), and polycythemia vera (PV) are myeloproliferative neoplasms (MPNs) that require precise molecular characterization. Although driver mutations such as BCR-ABL1 and JAK2 are diagnostically important, they do not fully explain disease heterogeneity. The NanoString nCounter® system enables direct multiplex gene expression analysis without RNA amplification and is suitable for degraded bone marrow specimens. This study aimed to analyze cytokine gene expression in bone marrow mononuclear cells of patients with MPNs and controls using NanoString technology, identify differentially expressed genes (DEGs) among MPN subtypes, and investigate their biological significance. Methods: Bone marrow aspirates were collected from 19 patients with MPNs (CML, ET, PMF, and PV) and 6 control patients. Mononuclear cells were isolated, and RNA expression of a 40-gene cytokine panel was analyzed using the NanoString nCounter® system with strict quality control and normalization. DEGs were identified for each MPN subtype, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses. Results: CML and PV demonstrated 20 and 12 DEGs, respectively. In contrast, ET showed only one DEG (IRAK2), and PMF showed none. Functional analyses revealed enrichment of cytokine signaling, Toll-like receptor (TLR), and JAK-STAT pathways in CML, indicating immune and inflammatory dysregulation. PV DEGs were associated with TLR signaling, IL-17 pathways, and cytokine-cytokine receptor interactions, suggesting active cytokine-mediated inflammation. Conclusions: CML and PV exhibited distinct cytokine-driven transcriptional signatures, whereas ET and PMF exhibited minimal alterations. These findings support the clinical utility of NanoString technology for bone marrow specimens and highlight disease-specific immune pathways as potential diagnostic biomarkers in MPNs.

Myeloid malignancies encompass a heterogeneous group of haematological disorders, primarily including myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs). MDS is characterised by defective myeloid cell maturation, while MPNs involve the pathological overproduction of myeloid lineage cells. In the absence of timely diagnosis and effective clinical intervention, both entities carry a substantial risk of progression to acute myeloid leukaemia (AML). Although allogeneic haematopoietic stem cell transplantation remains the only potentially curative therapy, its application is frequently constrained by patient-related factors such as advanced age and comorbid conditions. While currently, hypomethylating agent therapy (azacitidine and decitabine) is mainly used in high-risk MDS patients, and ruxolitinib is primarily used in symptomatic primary myelofibrosis (PMF-MPN), their clinical efficacy remains suboptimal. More recently, focus has turned toward the role of the tumour microenvironment (TME) in disease pathogenesis and whether therapeutically targeting the TME, either alone or in combination with conventional therapy, could present a new treatment option. Emerging evidence underscores the significant influence of TME components, particularly macrophages and T cells, in modulating immune responses and shaping the leukaemic niche to either facilitate or hinder malignant progression. In response, a new generation of immune checkpoint inhibitors are being developed to target the TME, including PD-1/CTLA-4 blockers, macrophage-directed agents including CD47 inhibitors, and T cell-targeting checkpoint inhibitors such as TIM-1 and LAG-3. This review will describe the functional role of key TME constituents in the progression of myeloid malignancies and explore the current landscape and future potential of advanced cellular and molecular immunotherapies in the treatment of these disorders.