Search Results (3,442)

Emperipolesis, a cell-in-cell phenomenon, involves a viable cell being transiently internalized within another cell’s cytoplasm from which it can exit without damaging either cell. In this report, we discuss the rarity of the emperipolesis of erythrocytes and erythroblasts, instead of the more commonly observed neutrophils. We report the case of a 52-year-old Chinese male who presented with pancytopenia and 33% blasts. Multiple mutations were revealed, including DNMT3A K826R, RUNX1 F396fs159, BCOR Q1208fs8, BCORL1 S575*, and PHF6 H302R. The patient was diagnosed with acute myeloid leukemia, myelodysplasia-related changes (AML-MR), and was treated with azacitidine and venetoclax, followed by daunorubicin and cytarabine (DA 3+7). This case highlights the rare occurrence of emperipolesis involving erythroid cells in AML-MR. We conducted a literature review exploring emperipolesis using PubMed, with search terms consisting of “emperipolesis”, “megakaryocytes”, “erythrocyte”, “erythroblast”, “neutrophil” and “lymphocyte”. A total of 24 articles that observed erythroid emperipolesis were referenced in this review, including 7 relevant case reports/series. Full article

Hematopoietic stem-cell transplantation (HSCT) has evolved from a salvage procedure for otherwise-fatal leukemia into a curative modality spanning nearly every hematological malignancy and several non-malignant disorders. The contemporary landscape has been reshaped by three converging forces: the refinement of disease-specific risk stratification (European LeukemiaNet [ELN] 2022 for acute myeloid leukemia, Molecular International Prognostic Scoring System [IPSS-M] for myelodysplastic syndromes, Mutation-Enhanced International Prognostic Scoring System [MIPSS70+ v2.0], and Myelofibrosis Transplant Scoring System [MTSS] for myelofibrosis); the integration of measurable residual disease (MRD) into dynamic, response-adapted transplant decisions; and the approval of immune effector cell therapies that have displaced transplantation from several long-standing indications while creating new ones (bridge-to-transplant, post-CAR-T consolidation). In parallel, post-transplant cyclophosphamide (PTCy) has largely equalized outcomes across matched sibling, matched unrelated, and mismatched alternative donors, and novel agents (ruxolitinib, belumosudil, axatilimab) have materially reduced graft-versus-host disease (GVHD) morbidity. This narrative review synthesizes current indications for autologous (auto-HSCT) and allogeneic (allo-HSCT) transplantations in adults, and flags areas of persistent controversy where randomized data are still maturing. Across all indications, the clinician’s question is shifting from “transplant or not?” towards “which donor, which conditioning, which bridge, and which post-transplant maintenance?”, each tailored to disease biology, MRD trajectory, and patient fitness. Full article

Background/Objectives: Novel (immune) therapies are needed to stabilize the disease or achieve remissions in AML. We already demonstrated that DCleus can be generated ex vivo from AML patients’ blasts in WB using approved drugs (GM-CSF and PGE-1 (Kit-M) or GM-CSF and Picibanil (OK-432), Kit-I). The generated DCleus induce antileukemia-directed immune cells of the adaptive and innate immune system, enabling leukemia-specific immune activation after MLC. Methods: We compared the effects of Kit-I vs. Kit-M by quantifying (1) their potential to produce DCs/DCleus from WB samples from 6 healthy individuals and 28 AML patients’ WB in different stages of the disease and (2) the activation of adaptive and innate leukemia-specific IFNγ-producing or degranulating antileukemic cells after MLC with and without Kit-I/Kit-M-pretreated WB. Furthermore, we correlated the obtained results with the achieved improved cells’ antileukemic functionality and patients’ clinical data. Results: In AML samples we found significantly higher frequencies of (mature) DCleus generable without induction of blast proliferation in Kit-M as well as (although less pronounced) in Kit-I-treated vs. untreated samples, a significant increase in the frequency of (leukemia- specific) immunoreactive cells, and improved blast cytotoxicity after MLC with Kit-M and with Kit-I-treated vs. untreated samples (potentially with higher induction of CD4 and CIK IFNγ + cells in Kit-I-pretreated samples). These data might suggest that both Kits work via different pathways. Conclusions: We show that Kit-M and Kit-I produce DCs/DCleus and subsequently enhance (potentially via a different mode of action) antileukemic immune cell activation after MLC. Our findings point to a possibility to enhance antileukemic treatment in vivo by combining agents or identifying criteria for selecting an appropriate agent (combination) for the respective patient in the course of a personalized treatment strategy. Full article

Background/Objectives: Hematological malignancies (HMs) are an important component of the cancer burden in adolescents and young adults (AYA, 15–39 years), requiring long-term specialized care. In Poland, recent healthcare reforms under the National Oncology Network (KSO) have not formally included haemato-oncology or AYA-specific needs. Methods: A population-based study was conducted using data from the Polish National Cancer Registry. AYAs diagnosed with HM between 2000 and 2022 were included. Descriptive analyses and projections were based on cases diagnosed between 2000 and 2022, whereas age-specific incidence trend analyses were restricted to the 2015–2022 period. Tumours were classified according to the HAEMCARE framework. Age-standardized incidence rates (ASIRs), annual percentage changes (APCs), and short-term projections through 2028 were estimated using generalized linear models. Additionally, data from the National Health Fund (NFZ) were analyzed to assess the geographical distribution of reimbursed drug programmes dedicated to selected HMs. Results: A total of approximately 23,000 AYA patients diagnosed with HMs were identified. Hodgkin lymphomas (HL) were the predominant tumour type across all age groups, while lymphoblastic leukemia/lymphoma was most common among younger AYAs and diffuse large B-cell lymphoma (DLBCL) increased in relative importance with age. Between 2015 and 2022, ASIRs remained stable only in two age groups (20–24 and 25–29), whereas statistically significant increases were observed among individuals aged 15–19, 30–34 and 35–39 years. Despite largely stable incidence patterns, projections indicated a growing absolute number of cases for DLBCL and follicular lymphomas. Analysis of NFZ data revealed substantial regional variation in the availability of reimbursed drug programmes, with up to six-fold differences in facility density between voivodships. Conclusions: HM epidemiology among AYAs in Poland is characterized by increasing incidence in selected lymphoma subtypes alongside declining mortality. Incorporating haemato-oncology and AYA-specific needs into national cancer planning frameworks should therefore be considered essential for future healthcare system preparedness. Full article

Background/Objectives: Patients receiving allogeneic hematopoietic stem cell transplantation (alloHCT) for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are at high risk for severe disease and treatment-related complications and toxicities. Pharmacogenetic studies suggest that genetic variants can alter the response to several drugs critical to alloHCT outcomes, including tacrolimus and cyclophosphamide, potentially impacting toxicity and treatment outcomes. Methods: To assess the frequency of pharmacogenetic variants in AML/ALL patients undergoing alloHCT, we used a validated 11-gene pharmacogenetic panel in an exploratory descriptive study. We retrospectively genotyped 142 AML/ALL patients including two atypical chronic myeloid leukemia (aCML) patients, ≥18 years, who underwent alloHCT at our center between January 2020 and June 2024. Results obtained from 470 individuals in the Lifelines NEXT population cohort were used as controls. Results: Almost all patients carried at least one pharmacogenetic variant (97.2%), with a mean of 3.2 (standard deviation = 1.5) variants per patient. Variants known to influence tacrolimus metabolism (CYP3A4 and CYP3A5) were present in 26.8% of patients. Variants known to influence cyclophosphamide metabolism (CYP2B6, CYP2C9, CYP2C19) were present in 81.7% of patients. Variant frequencies did not significantly differ from controls. Conclusions: Actionable pharmacogenetic variants are highly prevalent in alloHCT-recipients. Future studies should investigate whether genotype-guided drug selection and dosing could improve outcomes in alloHCT recipients. Full article

Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies. Serum galactomannan (GM) is widely used for diagnosis, but the prognostic value of the initial GM level is not well established. We aimed to assess the association between the initial serum GM level at IPA diagnosis and the radiological and clinical outcomes at 42 and 90 days. We retrospectively reviewed adult patients with hematological malignancies, including hematopoietic stem cell transplant (HSCT) recipients, diagnosed with proven or probable IPA at Sultan Qaboos University Hospital between 2014 and 2017, according to the 2008 EORTC/MSG criteria. Demographic, microbiological, radiological, and clinical data were collected. Outcomes were assessed using dichotomous and balanced multi-level GM cut-off categories. Seventy-eight patients were included. The median age was 44.5 years (range 18–76); 53.8% were male. Lymphoma (30.7%) and acute leukemia (25.6%) were the leading underlying diseases. Voriconazole was the most frequently used antifungal agent (74.3%). Prolonged neutropenia was present in 61.9%, and 30.7% had received HSCT. The mean serum GM at diagnosis was 1.95 (range 0.5–7.89). At 90 days, follow-up imaging showed a complete radiological response in 22 patients (29.3%), a partial response in 28 (37.3%), and no response in 25 (33.3%). Overall, 90-day mortality was 35.9%. There was no statistically significant association between initial GM level and 90-day mortality across categories (GM 0.5–3.0: 34.2% mortality; GM > 3.0: 60%; p = 0.243). Within the GM 0.5–3.0 group, complete radiological response was strongly associated with survival (95.2% alive at 90 days; p < 0.001). The initial serum GM level was not significantly associated with clinical or radiological outcomes at 42 or 90 days in patients with hematological malignancies and IPA. However, an early complete radiological response was strongly associated with improved survival, supporting the use of follow-up CT chest imaging to guide management. Full article

Pediatric acute myeloid leukemia (AML) is a highly heterogeneous malignancy, with cytogenetic and molecular abnormalities playing a critical role in determining prognosis and guiding treatment decisions. Despite therapeutic advances, patients with high-risk genetic mutations and translocations continue to experience suboptimal outcomes. As new targeted therapies emerge, the treatment of pediatric AML could undergo a paradigm shift, where “one-size-fits-all” chemotherapy is no longer the only frontline approach. Identifying genetic markers inform risk stratification and have greater impact on shaping the therapeutic approach, including the integration of targeted therapies such as FLT3 and menin inhibitors into frontline therapy. Furthermore, pediatric AML treatment options are being driven by recent discoveries in adult AML, broadening their clinical trials to include pediatric patients, in part due to the RACE for Children Act that went into effect in August 2020. This review identifies the most prevalent high-risk cytogenetic lesions in pediatric AML, emphasizing their incidence, prognostic significance, and implications for clinical management. By synthesizing current research on these key genetic abnormalities and their associated therapies, we aim to provide an updated perspective on the evolving landscape of high-risk pediatric AML management that can then lead to the establishment of an agile framework to rapidly evaluate, approve, and deploy novel agents. Full article

The bone marrow stromal microenvironment is damaged in patients with acute leukemia. The aim of this study was to analyze changes associated with the extracellular matrix, mitochondrial function, and vesicular transport in the proteome of multipotent mesenchymal stromal cells (MSCs) in patients at the onset, in remission, before, and 1–3 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The study included paired MSCs samples from the bone marrow of 12 patients at the onset and in remission of acute leukemia (4 ALL, 8 AML) and eight patients before and after allo-HSCT (4 ALL, 4 AML). MSCs from eight healthy donors were used as a control. The growth characteristics and the proteome subsets describing extracellular matrix, mitochondria, and vesicular formation were studied. The proteome of the patients’ MSCs differed significantly from that of the donor MSCs, both at the onset and in remission. Changes noted in the composition of extracellular matrix proteins may affect cell adhesion and access to growth factors. Significant changes were revealed in proteins affecting mitochondrial function. Vesicular transport proteins also differed between the donor and patient groups. Unexpectedly, no differences were found between the MSCs of donors and patients before and after allo-HSCT. Full article

B cell aplasia (BCA), the sustained depletion of circulating CD19-positive B cells, is the defining on-target, off-tumor consequence of anti-CD19 chimeric antigen receptor (CAR) T cell therapy. Despite its occurrence across all approved CAR T cell products and all responding patients, BCA has not been systematically reviewed as a standalone clinical and biological phenomenon. This review synthesizes data from landmark trials and real-world cohorts across B cell-acute lymphoblastic leukemia (B-ALL), large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia to characterize BCA incidence, recovery kinetics, prognostic significance, and management implications. Anti-BCMA products, which mechanism of action differs fundamentally, depleting plasma cells rather than B cell precursors, are intentionally excluded from this review. BCA is observed in all responders and is consistently absent in non-responders across reported cohorts , making it a reliable pharmacodynamic marker of CAR T cell activity. Its prognostic significance is disease-specific: in lymphoma, BCA recovery does not predict relapse and durable remission is achievable independent of sustained aplasia; in B-ALL, early BCA recovery within six months is a robust independent predictor of CD19-positive relapse, while persistent BCA correlates with sustained remission. CD19-negative antigen-escape relapse occurs preferentially in the presence of intact BCA and high pre-infusion tumor burden. Combining BCA kinetics with bone marrow next-generation sequencing minimal residual disease assessment at day 28 and month 3 constitutes the most powerful post-infusion risk-stratification framework currently available. BCA is mechanistically dissociated from hypogammaglobulinemia: IgM declines rapidly and profoundly, IgA more slowly, while IgG—maintained by CD19-negative long-lived plasma cells—is the most preserved isotype. No B cell count threshold below which hypogammaglobulinemia becomes clinically significant has been established. Evidence-informed IVIG replacement thresholds are proposed, though no randomized trial data exist to support them, representing a critical gap requiring prospective investigation. Full article

Background/Objectives: Juvenile myelomonocytic leukemia (JMML) is a rare, highly aggressive form of pediatric myelodysplastic/myeloproliferative neoplasm characterized by molecular heterogeneity and constitutive activation of the RAS signaling pathway. This study aimed to characterize the mutational landscape, driver genes, mutational signatures, functional pathways, and therapeutic potential of mutated epigenetic regulator genes in JMML. Methods: Tumor and matched buccal swab samples were collected from 35 JMML patients, and whole-exome sequencing was performed. Somatic variants were called with GATK-Mutect2 and annotated with ANNOVAR. maftools and OncodriveCLUST were used for mutational profiling, co-occurrence analysis, driver gene identification, and protein domain mapping. Drug–gene interactions were explored using DGIdb, mutational signatures for genes were characterized by MutationalPatterns, and functional enrichment analysis was performed by the clusterProfiler package. Results: A total of 28 variants were detected in epigenetic regulator genes, with missense mutations being the most common class of variants and a C>T nucleotide substitution pattern being the most frequent. EP300, SETD2, and DNMT3B were the genes most frequently altered, with 8.57% of cases each, followed by ASXL1, BCORL1, ATRX, KMT2A, and TET2 (5.71% each). Driver gene analysis identified ASXL1 as the top candidate driver gene, followed by BCORL1, EP300, and SETD2. Functional enrichment analysis revealed a high number of genes involved in chromatin organization, histone modification, transcriptional regulation, and oncogenic signaling pathways. The mutational signatures identified were SBS5-like, which are dominated by C>T and T>C transitions, indicating endogenous mutational processes. Analysis of drug–gene interactions revealed KMT2A, EP300, and ATRX as the most interconnected and potentially actionable therapeutic targets. Conclusions: This study provides a comprehensive characterization of epigenetic regulator gene alterations in JMML and highlights the importance of epigenetic dysregulation in disease pathogenesis. Full article

Background/Objectives: Ibrutinib is an established treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), but its use commonly occurs in older patients with polypharmacy, cardiovascular comorbidity and infection vulnerability. CYP3A-modifying drugs and antithrombotic agents are clinically actionable co-exposure domains because they may alter ibrutinib exposure, bleeding risk or the management of atrial arrhythmia. This study evaluated post-marketing reporting patterns for these co-exposures in FAERS. Methods: Adult FAERS reports through 25Q2 with ibrutinib exposure and CLL/SLL-compatible indications were analyzed after false-positive indication captures were removed. Co-exposures were defined at report level using prespecified drug dictionaries, and grouped adverse-event reporting was evaluated using reporting odds ratio, proportional reporting ratio, chi-square and an information-component-style two-by-two metric. Results: The final cohort comprised 20,878 adult CLL/SLL + ibrutinib reports. CYP3A modifier co-exposure was present in 1373 reports (6.6%), and antithrombotic co-exposure in 3701 reports (17.7%). Antithrombotic exposure increased with age, from 9.8% in reports aged 18–64 years to 23.2% in reports aged ≥75 years. CYP3A modifier exposure was associated with enriched reporting of infection and cytopenia phenotypes, particularly severe infection-like events with CYP3A inhibitors and inducers. Antithrombotic exposure showed consistent reporting enrichment for atrial arrhythmia, bleeding and major bleeding-like events, with the strongest grouped signals among anticoagulant-exposed reports. Overlap analyses showed that the co-exposure domains were not mutually exclusive. Conclusions: These findings should be interpreted as reporting disproportionality rather than incidence or causal risk, but they support prioritizing CYP3A-modifying drugs and antithrombotic therapy during medication reconciliation, interaction screening and risk mitigation in older patients receiving ibrutinib. Full article

Background/Objectives: Childhood cancer outcomes are influenced by clinical, socioeconomic, and territorial factors, particularly in resource-limited settings. This study characterized pediatric cancer patients from Córdoba and Sucre, Colombia, and evaluated factors associated with clinical outcomes in a regional referral center. Methods: A retrospective hospital-based study included 434 patients aged 0–18 years diagnosed between 2018 and 2024. Sociodemographic, clinical, and territorial socioeconomic variables were analyzed using the Multidimensional Poverty Index (MPI). Clinical outcomes were classified as favorable, non-favorable, or death. Firth-penalized logistic regression models were used to assess adjusted associations. Results: Hematologic malignancies predominated (65.9%), with acute lymphoblastic leukemia as the most frequent diagnosis. Most patients came from municipalities with moderate or high multidimensional poverty (85.2%), and the rural territories of origin showed greater deprivation in education, employment, housing, water access, and sanitation. Favorable outcomes occurred in 82.9% of patients, while 8.5% had non-favorable outcomes and 8.5% died. Older age and non-hematologic malignancies were associated with non-favorable outcomes. Mortality was associated with older age, subsidized health insurance, and non-hematologic malignancies. MPI and rural residence were not independently associated with outcomes after adjustment. Conclusions: Although MPI was not independently associated with clinical outcomes, it identified substantial territorial deprivation. Integrating clinical and territorial indicators may support equity-oriented surveillance and pediatric oncology interventions. Full article

We study an optimal control framework for chemotherapy administration in patients with chronic lymphocytic leukemia (CLL) while accounting for immune regulation and treatment-induced allergic reactions. The analysis is based on a previously developed nonlinear delay differential equation model describing the interactions between leukemic cells, immune populations, antigen-presenting cells, and cytokine dynamics, with three distinct biological delays. The chemotherapy infusion rate is introduced as a time-dependent control variable and optimized to reduce leukemic burden, shift the helper T-cell balance toward a Th1-dominant configuration associated with lower hypersensitivity risk, and preserve immune competence. Existence of an optimal control is established for arbitrary delays and horizon, without the commensurability hypothesis required by reductions in delay systems to higher-dimensional delay-free ones; the argument uses only that the control enters the dynamics affinely and the running cost concavely. Necessary optimality conditions are derived via Pontryagin’s Maximum Principle for systems with delays, and the resulting eleven-dimensional adjoint system, which carries advanced arguments generated by the three delays, is written out explicitly. A contraction estimate for the associated sweep operator yields both uniqueness of the optimal control on a short horizon and geometric convergence of the numerical scheme. The optimality system is solved by a forward–backward sweep adapted to the delayed setting, with documented convergence and grid independence and sensitivity analysis over kinetic parameters, delays, initial conditions and objective weights. The optimized schedule is compared not only with the untreated case and a low constant dose, but also with a constant infusion delivering the same cumulative exposure, so that the reported benefit is attributable to the temporal distribution of the dose rather than to its total amount. At equal exposure, the optimal schedule reaches each therapeutic milestone earlier—Th1 dominance 0.9 days sooner and a 90% leukemic reduction 1.6 days sooner—and attains a terminal leukemic burden lower by a factor of 2.25; a constant infusion of the same total dose reaches a comparable configuration later. The benefit of adaptive scheduling in this model is therefore principally one of rate of response at fixed drug exposure. We emphasize that the absolute Th2 population is not reduced by treatment; the reduction in hypersensitivity risk arises from the resulting Th1-dominant relative balance rather than from direct Th2 suppression. To characterize the therapeutic outcome in information-theoretic terms, we describe the two competing goals as distributional balances: an allergy axis, given by the Th1/Th2/Treg distribution, and a leukemia axis, given by the immune/leukemic distribution, each measured by its Shannon entropy and its Kullback–Leibler divergence to a healthy reference profile. These quantities are used in two roles. As diagnostics, they are evaluated along the computed trajectories, and the ordering of dosing strategies is shown to be robust across twenty alternative reference profiles. As an objective, the combined divergence is then taken as the running cost of a second optimal control problem; because it depends on the leukemic population only through a normalized fraction, it prescribes a markedly gentler schedule that administers 37% of the drug and still achieves a 93% leukemic reduction, against 98% for the population-based formulation. These results suggest that adaptive, immune-aware chemotherapy scheduling may accelerate disease control at fixed drug exposure, and that information-theoretic objectives offer a scale-free alternative formulation of the therapeutic goal. Full article

Background/Objectives: Revolutionary small molecule, targeted, tyrosine kinase inhibitors (TKIs) in the clinic have engendered the perception that optimal treatment has already been established for diseases like chronic myeloid leukemia (CML). Addressing BCR::ABL1 oncokinase domain mutations in CML is unlikely to redress disease recrudescence owing to persistent leukemia stem cells (LSCs). Therefore, it is necessary to consider an alternative strategic approach: disrupting LSC interactions with the protective microenvironment and/or immune system. The interaction of the TNF-α superfamily member, CD27, with its upregulated ligand, CD70, initiates survival signaling specifically in CML cells when BCR::ABL1 is inhibited by TKIs and thus represents an attractive target. Previous studies modulating the expression of CD27 on LSCs in a mouse model of advanced phase CML were encouraging. In our study, we explored the CD70/CD27 axis as a therapeutic target in early-phase disease. Methods: Primitive CD34+ cells from treatment-naïve chronic phase (CP) CML patients were drug-exposed in an in vitro co-culture system; combination drug treatments of the therapeutic anti-CD70 antibody and TKIs, nilotinib, were assessed in our CP CML murine model. Results: The blockade of the CD70/CD27 axis in combination with TKIs did not result in greater LSC elimination than with nilotinib as a single agent in our CP CML models. Nonetheless, there was an observed reduction in CD70+ cells with combination treatment. Conclusion: Further preclinical study of the antibody as an adjunct in CD70-expressing hematological malignancy is perhaps warranted. Full article

Background/Objectives: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders driven by somatic mutations, most commonly those in JAK2, CALR, and MPL. While conventional molecular testing often focuses on these canonical mutations, emerging data suggest that additional mutations and low-variant-allele-frequency (VAF) subclones may contribute to disease progression and prognosis. Methods: We applied ultra-deep targeted sequencing with an error-correction algorithm to analyze bone marrow and peripheral blood samples from 134 patients with essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF), secondary myelofibrosis (MF), or post-MPN acute leukemia. Targeted sequencing panels were used to detect disease-associated and clonal driver mutations. Matched germline controls were not systematically available. Results: Low-VAF variants (<5%) were identified in 4/16 (25%) CALR, 3/7 (43%) MPL, and 9/11 (82%) TP53 mutations. In contrast, all TP53 mutations identified at leukemic transformation had VAFs > 5%, suggesting clonal expansion during progression. Paired sequencing at initial MPN diagnosis and leukemic transformation was available for three patients. JAK2 p.V617F VAFs differed according to treatment timing (Kruskal–Wallis test, p = 0.0138), with lower VAFs observed in untreated patients; however, this association may be influenced by treatment-selection confounding. Mutations in ASXL1 and SRSF2 were occasionally observed in ET and secondary MF, although their prognostic significance remains uncertain. Progression analyses were exploratory because of the limited number of events and longitudinally sampled patients, and formal survival or prognostic modeling was not performed. Conclusions: Ultra-deep error-corrected sequencing enables sensitive detection of low-VAF mutations in MPNs, including subclonal events potentially missed by less sensitive assays. These findings demonstrate the potential utility of high-sensitivity panel-based sequencing for molecular characterization of MPN, while larger longitudinal studies are required to establish the prognostic and clinical significance of these findings. Full article