Myelofibrosis (MF) splenomegaly reflects not only extramedullary hematopoiesis (EMH) but a compartmental organization of the splenic microenvironment into spatially distinct niches. Using Spatial whole transcriptome profiling on FFPE spleen tissue from three MF patients, we interrogated three anatomically defined compartments: Intravascular (IV), Perivascular (PV) and Red Pulp (RP). Differential expression was estimated through pairwise compartment contrasts with Benjamini-Hochberg false discovery rate correction (FDR < 0.05, |log2FC|≥1), and compartment “core signatures” were defined by directional concordance across the two contrasts relevant to each compartment. IV regions of interest (ROIs) showed an endothelial/adhesion and vascular stress program (e.g., PECAM1, VCAM1; antioxidant enzymes). PV ROIs were characterized by fibro-remodeling and immune-structured signals (COL1A1/COL3A1, LOXL1, MMP2/TIMP1; HLA‑DRA/CD74) including CXCL12, consistent with a PV niche coupling extracellular matrix remodeling to hematopoietic retention cues. RP ROIs captured an EMH-associated erythroid/heme program (ALAS2, FECH, BLVRB) with stress and inflammatory alarmins (S100A8/S100A9). Together, these findings support a compartmental “division of labor” in MF spleen, vascular interface activation, PV remodeling/chemokine niches, and RP EMH/redox stress, providing a spatial framework to interpret splenomegaly as structured niche dependencies and to prioritize candidate microenvironmental dependencies for follow‑up validation.

Down syndrome (DS) confers a developmentally rooted predisposition to both myeloid and lymphoid leukemias, particularly myeloid leukemia associated with DS (ML-DS) and acute lymphoblastic leukemia associated with DS (ALL-DS). While trisomy 21-driven gene dosage imbalance is central to this risk, DS leukemogenesis cannot be fully explained by recurrent mutations alone; it reflects a dynamic interplay between altered hematopoietic development, cell-intrinsic programs, and tissue microenvironmental cues. In this perspective, we argue that the field should move beyond cataloging cellular heterogeneity and adopt a topographic, multi-omic framework of DS leukemogenesis. We discuss how fetal niche biology shapes pre-leukemic evolution in ML-DS, including the developmental context of GATA1-mutant clones, and how therapy-driven bottlenecks may promote persistence of spatially protected residual disease in ALL-DS. We further highlight the translational potential of integrating spatially resolved transcriptomics with single-cell and protein-aware multi-omics to identify compartment-specific signaling programs and clinically actionable vulnerabilities. A spatially informed model of DS leukemia may improve biological stratification, clarify mechanisms of relapse and toxicity, and support the development of more effective and less toxic therapeutic strategies.

The growing demand for precision diagnostics in cystic fibrosis and other genetic disorders, such as cancers, is driving the need for sequencing platforms that combine analytical robustness, scalability, and cost-efficiency. In this study, we performed a direct comparison between two leading Next-Generation Sequencing (NGS) platforms, MiSeq (Illumina, CA, USA) and DNBSEQ-G99RS (MGI Tech Co., Shenzhen, China), using a CE-IVD-certified CFTR panel (Devyser AB), selected for its complexity and variant spectrum, including SNVs, CNVs, and intronic polymorphisms. A total of 47 genomic DNA samples from routine clinical activity were analyzed on both platforms. Illumina sequencing covered all CFTR variants using standard workflows, while MGI data were generated from residual diagnostic DNA, with informed consent. Sequencing data were processed using Amplicon Suite v3.7.0 for variant calling, annotation, and ACMG classification. Quality control metrics and platform-specific parameters were also evaluated. Both platforms demonstrated complete concordance in variant detection, including SNVs, CNVs, and complex alleles (e.g., Poly-T/TG). Illumina exhibited slightly superior basecalling quality and allelic frequency uniformity, while MGI achieved higher sequencing depth (mean ~2793×) and demultiplexing efficiency. No false positives, false negatives, or discordant HGVS annotations were observed. The use of full-gene CFTR sequencing enabled granular and technically rigorous cross-platform validation. These findings confirm the analytical equivalence of Illumina and MGI for diagnostic genotyping. Moreover, MGI's greater data output and flow cell capacity may offer tangible advantages in high-throughput settings, including somatic applications such as liquid biopsy and molecular oncology workflows.

Myelofibrosis (MF) is a complex myeloproliferative neoplasm characterized by abnormal hematopoietic stem cell proliferation and subsequent bone marrow (BM) fibrosis. First documented in the late 19th century, MF has since been extensively studied to unravel its pathophysiology, clinical phenotypes, and therapeutic interventions. MF can be classified into primary and secondary forms, both driven by mutations in genes such as JAK2, CALR, and MPL, which activate the JAK-STAT signaling pathway. These driver mutations are frequently accompanied by additional non-driver mutations in genes like TET2, SRSF2, and TP53, contributing to disease complexity. The BM microenvironment, consisting of stromal cells, extracellular matrix, and cytokines such as TGF-β and TNF-α, plays a critical role in fibrosis and aberrant hematopoiesis. Clinically, MF manifests with symptoms ranging from anemia, splenomegaly, and fatigue to severe complications such as leukemic transformation. Splenomegaly, caused by extramedullary hematopoiesis, leads to abdominal discomfort and early satiety. Current therapeutic strategies include JAK inhibitors like Ruxolitinib, which target the JAK-STAT pathway, alongside supportive treatments such as blood transfusions, erythropoiesis-stimulating agents and developing combinatorial approaches. Allogeneic hematopoietic stem cell transplantation remains the only curative option, though it is limited to younger, high-risk patients. Recently approved JAK inhibitors, including Fedratinib, Pacritinib, and Momelotinib, have expanded the therapeutic landscape. Spatially Resolved Transcriptomics (SRT) has revolutionized the study of gene expression within the spatial context of tissues, providing unprecedented insights into cellular heterogeneity, spatial gene regulation, and microenvironmental interactions, including stromal-hematopoietic dynamics. SRT enables high-resolution mapping of gene expression in the BM and spleen, revealing molecular signatures, spatial heterogeneity, and pathological niches that drive disease progression. These technologies elucidate the role of the spleen in MF, highlighting its transformation into a site of abnormal hematopoietic activity, fibrotic changes, and immune cell infiltration, functioning as a “tumor surrogate.” By profiling diverse cell populations and molecular alterations within the BM and spleen, SRT facilitates a deeper understanding of MF pathophysiology, helping identify novel therapeutic targets and biomarkers. Ultimately, integrating spatial transcriptomics into MF research promises to enhance diagnostic precision and therapeutic innovation, addressing the multifaceted challenges of this disease.

The molecular basis of Down syndrome (DS) predisposition to leukemia is not fully understood but involves various factors such as chromosomal abnormalities, oncogenic mutations, epigenetic alterations, and changes in selection dynamics. Myeloid leukemia associated with DS (ML-DS) is preceded by a preleukemic phase called transient abnormal myelopoiesis driven by GATA1 gene mutations and progresses to ML-DS via additional mutations in cohesin genes, CTCF, RAS, or JAK/STAT pathway genes. DS-related ALL (ALL-DS) differs from non-DS ALL in terms of cytogenetic subgroups and genetic driver events, and the aberrant expression of CRLF2, JAK2 mutations, and RAS pathway-activating mutations are frequent in ALL-DS. Recent advancements in single-cell multi-omics technologies have provided unprecedented insights into the cellular and molecular heterogeneity of DS-associated hematologic neoplasms. Single-cell RNA sequencing and digital spatial profiling enable the identification of rare cell subpopulations, characterization of clonal evolution dynamics, and exploration of the tumor microenvironment’s role. These approaches may help identify new druggable targets and tailor therapeutic interventions based on distinct molecular profiles, ultimately improving patient outcomes with the potential to guide personalized medicine approaches and the development of targeted therapies.

Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard “one size fits all” treatment approach included intensive chemotherapy treatment with anthracyclines and cytarabine. The manuscript first traces the evolution of the understanding of the pathology from the 1970s to the present. The enormous strides made in its categorization prove to be crucial for risk stratification, enabling an increasingly personalized diagnosis and treatment approach. Subsequently, we highlight how, over the past 15 years, technological advances enabling single cell RNA sequencing and T-cell modification based on the genomic tools are affecting the classification and treatment of AML. At the dawn of the new millennium, the advent of high-throughput next-generation sequencing technologies has enabled the profiling of patients evidencing different facets of the same disease, stratifying risk, and identifying new possible therapeutic targets that have subsequently been validated. Currently, the possibility of investigating tumor heterogeneity at the single cell level, profiling the tumor at the time of diagnosis or after treatments exist. This would allow the identification of underrepresented cellular subclones or clones resistant to therapeutic approaches and thus responsible for post-treatment relapse that would otherwise be difficult to detect with bulk investigations on the tumor biopsy. Single-cell investigation will then allow even greater personalization of therapy to the genetic and transcriptional profile of the tumor, saving valuable time and dangerous side effects. The era of personalized medicine will take a huge step forward through the disclosure of each individual piece of the complex puzzle that is cancer pathology, to implement a “tailored” therapeutic approach based also on engineered CAR-T cells.

Hereditary erythrocytosis is a rare hematologic disorder characterized by an excess of red blood cell production. Here we describe a European collaborative study involving a collection of 2,160 patients with erythrocytosis sequenced in ten different laboratories. We focused our study on the EGLN1 gene and identified 39 germline missense variants including one gene deletion in 47 probands. EGLN1 encodes the PHD2 prolyl 4-hydroxylase, a major inhibitor of hypoxia-inducible factor. We performed a comprehensive study to evaluate the causal role of the identified PHD2 variants: (i) in silico studies of localization, conservation, and deleterious effects; (ii) analysis of hematologic parameters of carriers identified in the UK Biobank; (iii) functional studies of the protein activity and stability; and (iv) a comprehensive study of PHD2 splicing. Altogether, these studies allowed the classification of 16 pathogenic or likely pathogenic mutants in a total of 48 patients and relatives. The in silico studies extended to the variants described in the literature showed that a minority of PHD2 variants can be classified as pathogenic (36/96), without any differences from the variants of unknown significance regarding the severity of the developed disease (hematologic parameters and complications). Here, we demonstrated the great value of federating laboratories working on such rare disorders in order to implement the criteria required for genetic classification, a strategy that should be extended to all hereditary hematologic diseases.

The identification of prognostic factors for aggressive B-cell lymphomas still represents an unmet clinical need. We used forward phase protein arrays (FFPA) to identify proteins associated with overall survival (OS) from diagnostic formalin-fixed paraffin-embedded material of diffuse large B-cell lymphoma (DLBCL) patients (n = 47). Univariate Cox regression analysis identified numerous proteins, including immune check-point molecules (PDCD1, PDCD2 and PD1L2) and BCL2 to be significantly associated with OS. However, only ETV6 and PIM2 proteins persisted following multivariate Cox analysis. Independent validation studies by immunohistochemistry and analysis of public gene expression profiles of DLBCL confirmed a prognostic role for high ETV6 and ETV6/PIM2 ratios in DLBCL. ETV6 is a recurrently mutated/deleted gene in DLBCL for which its function in this disease entity is currently unknown. We find that ETV6 is upregulated during oncogenic transformation of germinal center B-cells and that it regulates DLBCL survival, as its acute loss results in marked apoptosis. Fluctuations in survivin (BIRC5) expression levels were associated with this phenomenon. Furthermore, an inverse correlation between ETV6 and BIRC5 expression levels was found and correlated with a response to the BIRC5 inhibitor, YM155. In conclusion, we present evidence for an oncogenic function of ETV6 in DLBCL.

Acute leukemias, classified as acute myeloid leukemia and acute lymphoblastic leukemia, represent the most prevalent hematologic tumors in adolescent and young adults. In recent years, new challenges have emerged in order to improve the clinical effectiveness of therapies already in use and reduce their side effects. In particular, in this scenario, metabolic reprogramming plays a key role in tumorigenesis and prognosis, and it contributes to the treatment outcome of acute leukemia. This review summarizes the latest findings regarding the most relevant metabolic pathways contributing to the continuous growth, redox homeostasis, and drug resistance of leukemia cells. We describe the main metabolic deregulations in acute leukemia and evidence vulnerabilities that could be exploited for targeted therapy.

Abstract Background [-2]proPSA seems to outperform free/total prostate-specific antigen (PSA) ratio in prostate cancer diagnosis. However, [-2]proPSA stability remains an underestimated issue. We examined [-2]proPSA stability over time in whole blood before separation of serum and plasma and its implications for prostate health index (Phi) determination. Total PSA (tPSA) and free PSA (fPSA) stabilities were also assessed. Methods Blood was drawn from 26 patients and separated in two tubes for plasma (K2EDTA and K2EDTA plus protease inhibitors – P100) and one for serum (clot activator plus gel separator). Tubes were stored at room temperature before centrifugation 1, 3 and 5 h for serum and EDTA plasma or 1 and 5 h for P100 plasma. To investigate the influence of gel separator on markers’ stability, blood was collected from 10 patients in three types of tubes to obtain serum: tubes with clot activator plus gel separator, with silica particles or glass tubes. Biomarkers were assayed with chemiluminescent immunoassays. Results [-2]proPSA and Phi levels significantly and progressively increased over time in serum (+4.81% and +8.2% at 3 h; +12.03% and +14.91% at 5 h, respectively, vs. 1 h; p<0.001). Conversely, [-2]proPSA levels did not change in plasma (EDTA or P100). tPSA levels did not change over time in serum or plasma, whereas fPSA decreased in serum. All markers were higher in plasma than in serum at any time point. This difference did not seem to be attributable to the use of gel for serum preparation. Conclusions EDTA prevented spurious in vitro modifications in PSA-related isoforms, confirming that a stabilized blood sample is a prerequisite for [-2]proPSA measurement and Phi determination.

OBJECTIVE:To investigate the prevalence and type of thrombotic events reported in patients with congenital factor XI (FXI) or factor VII (FVII) deficiency.PATIENTS AND METHODS:Data on all patients with congenital FXI or FVII deficiency and a thrombotic event were gathered by means of a time unlimited PubMed search carried out in June 2014 and in February 2015. Appropriate keywords including the medical subject headings were used in both instances. Side tables were also consulted and cross-checking of the references was carried out to avoid omissions. The thrombosis event had to be proven by objective methods.RESULTS:Forty-three patients with FXI deficiency had arterial thrombosis and only eight had venous thrombosis. On the contrary, only five patients with FVII deficiency had arterial thrombosis whereas 31 patients had venous thrombosis. The arterial/venous ratios were 5.37 and 0.17 for FXI or FVII, respectively.CONCLUSIONS:Arterial thrombosis is frequent in FXI deficiency whereas venous thrombosis is rare. The reverse is true for FVII deficiency. The significance of these findings is discussed especially in view of the recent use of synthetic anti-FXI compounds in the prophylaxis of post-orthopedic surgery of venous thrombosis complications.

Bradford, P.T., Devesa, S.S., Anderson, W.F. & Toro, J.R. (2009) Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood, 113, 5064–5073. Burt, R.K., Guitart, J., Traynor, A., Link, C., Rosen, S., Pandolfino, T. & Kuzel, T.M. (2000) Allogeneic hematopoietic stem cell transplantation for advanced mycosis fungoides: evidence of a graft-versus-tumor effect. Bone Marrow Transplantation, 25, 111–113. Canninga-van Dijk, M.R., Sanders, C.J., Verdonck, L.F., Fijnheer, R. & van den Tweel, J.G. (2003) Differential diagnosis of skin lesions after allogeneic haematopoietic stem cell transplantation. Histopathology, 42, 313–330. Favre, A., Cerri, A., Bacigalupo, A., Lanino, E., Berti, E. & Grossi, C.E. (1997) Immunohistochemical study of skin lesions in acute and chronic graft versus host disease following bone marrow transplantation. The American Journal of Surgical Pathology, 21, 23–34. Heldal, D., Brinch, L., Evensen, S.A., Tjonnfjord, G.E., Aamodt, G., Elgjo, K. & Sviland, L. (2004) Skin biopsies for early diagnosis and prognosis of graft-versus-host disease in recipients of allogeneic stem cells from blood or bone marrow. Bone Marrow Transplantation, 34, 345–350. Hilgendorf, I., Greinix, H., Halter, J.P., Lawitschka, A., Bertz, H. & Wolff, D. (2015) Long-term follow-up after allogeneic stem cell transplantation. Deutsches € Arzteblatt International, 112, 51–58. Hosing, C., Bassett, R., Dabaja, B., Talpur, R., Alousi, A., Ciurea, S., Popat, U., Qazilbash, M., Shpall, E.J., Oki, Y., Nieto, Y., Pinnix, C., Fanale, M., Maadani, F., Donato, M., Champlin, R. & Duvic, M. (2015) Allogeneic stem-cell transplantation in patients with cutaneous lymphoma: updated results from a single institution. Annals of Oncology: Official Journal of the European Society for Medical Oncology/ESMO, 26, 2490–2495. Lechowicz, M.J., Lazarus, H.M., Carreras, J., Laport, G.G., Cutler, C.S., Wiernik, P.H., Hale, G.A., Maharaj, D., Gale, R.P., Rowlings, P.A., Freytes, C.O., Miller, A.M., Vose, J.M., Maziarz, R.T., Montoto, S., Maloney, D.G. & Hari, P.N. (2014) Allogeneic hematopoietic cell transplantation for mycosis fungoides and Sezary syndrome. Bone Marrow Transplantation, 49, 1360– 1365. Sloane, J.P., Elliott, C.J. & Powles, R. (1988) HLADR expression in epidermal keratinocytes after allogeneic bone marrow transplantation. Relationship to histology, rash, marrow purging, and systemic graft-versus-host disease. Transplantation, 46, 840–844. Wingard, J.R., Majhail, N.S., Brazauskas, R., Wang, Z., Sobocinski, K.A., Jacobsohn, D., Sorror, M.L., Horowitz, M.M., Bolwell, B., Rizzo, J.D. & Soci e, G. (2011) Long-term survival and late deaths after allogeneic hematopoietic cell transplantation. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 29, 2230–2239.

Idiopathic erythrocytosis (IE) is an absolute erythrocytosis with no known cause, diagnosed by exclusion of primary and secondary erythrocytosis. Familial erythrocytosis (FE) is a rare disease and as the rare patients with JAK2-wild-type polycythemia vera (PV) may be misdiagnosed as IE. We compared 78 patients with IE, 21 with FE and 136 with PV in the effort to identify simple features capable of discriminating between them. FE patients were younger at diagnosis either than IE and PV (p < 0.001); IE and FE had lower WBC, platelet counts and higher serum EPO levels, and had splenomegaly and thrombotic events less frequently than PV patients. Phlebotomies to obtain a haematocrit lower than 45 % induce platelet count increase in 70 % of PV but not in IE. Mainly in men, normal spleen, normal platelet counts and no history of thrombosis at diagnosis argue against PV; diagnosis of IE could be supported by means of a cycle of venesection to see how it affects their platelet count. No simple data capable of distinguishing between IE and FE were identified; therefore, a case of sporadic erythrocytosis in a young patient should be investigated as a possible genetic cause.

Pulmonary embolism is a complication of deep vein thrombosis. It occurs in the population with a normal clotting mechanism, but it may also occur in patients with congenital bleeding conditions. Here, we report on all cases of pulmonary embolism in congenital hemorrhagic disorders. All reported cases of pulmonary embolism in congenital coagulation disorders have been gathered by a time-unlimited PubMed search. Cross-checking of the references listed at the end of the single papers was carried out to avoid omissions. Seventy-two patients had an objectively demonstrated pulmonary embolism. The event occurred in patients with fibrinogen, factor V, factor VIII (FVII), FVIII, FIX, and FXI deficiency, and in those with von Willebrand's disease. No embolism was reported in FII, factor X, and FXIII deficiency. Thirty were women and 28 were men, whereas in the remaining 14 cases, sex was not reported. Age varied from 6 to 81 years (mean age 34.3 years). The management varied from only supportive to the administration of unfractionated heparin, low-molecular-weight heparin, and anti-vitamin K medications, accompanied by adequate replacement therapy. Evolution was fair or good in the majority of cases, but there were 10 fatalities. Risk factors were present in 61 patients. The most frequent of these were replacement therapy (35 cases), surgery (34), and old age (13). Some patients had more than one risk factor. Eleven patients had no risk factors. There are discrepancies in the prevalence of pulmonary embolism among different clotting disorders. The conditions most frequently affected are FVII deficiency and fibrinogen defects. The significance of the findings is discussed.

Congenital Erythrocytosis (CE) are rare and heterogeneous clinical entities. They are caused by genetic deregulation of the erythroid production resulting in increased production of red blood cells (RBCs). Primary Congenital Familial Polycythemia (PCFP) is due to erythropoietin receptor (EPOR) mutations and is associated with reduced levels of serum erythropoietin (EPOs). Secondary CE are characterized by high EPOs levels, may be due to mutations of the oxygen-sensing pathway (OSP) genes: von Hippel-Lindau (VHL), hypoxia-inducible factor 2 alpha (HIF2A/EPAS1) and prolyl hydroxylase 2 (EGLN1/PHD2). Within 106 patients followed in our centre with sporadic not myeloproliferative erythrocytosis we found 9 mutations (8,5%) in the involved genes. Here we report the functional studies of 1 novel PHD2 (c.1045G>A) and of 2 EPOR gene missense mutations (c.1013G>A and c.1022C>T). To evaluate the HIF transcriptional activity of PHD2 mutation, an in cellulo reporter assay has been performed, while the hydroxylation capacity of PHD2 variants has been tested with an in vitro Hydroxylation test. PHD2 variant does not show a clear loss-of-function of the PHD2 proteins. More sensitive tests could be developed and other PHD2 partners may be tested in this patient. The activation of EPOR mutated signaling was evaluated with a kinetic assay using transfected K562 cell lines. The EPOR signaling cascade results more active in mutated cells than in the WT cells when stimulated with EPO as shown by higher phosphorylation of STAT5 and ERK. Both mutations impair the C-terminal negative regulatory domain and determine gain-of-function in the EPOR signalling cascade. These are the first missense mutations of EPOR with a functional demonstrated activity that affect the EPOR signaling cascade. Other candidate genes need to be investigated to completely understand the ethiology of high hematocrit (HCT) level both in congenital and sporadic erythrocytosis

OBJECTIVE:To investigate the occurrence of ischemic stroke in patients with congenital bleeding disorders. PATIENTS AND METHODS:Patients with congenital bleeding disorders who presented an objectively proven ischemic stroke were obtained by means of a time unlimited Pubmed search. Appropriate key words and Medical subject headings were used. Cross-checking of the references was also carried out. RESULTS:There were four cases of Fibrinogen defects or Factor VII deficiency; seven patients had Hemophilia (6 hemophilia A and 1 hemophilia B); eight cases of FXI deficiency and six patients with von Willebrand Disease. One patient had a congenital platelet disorder. Age varied from 7 to 80 (mean age 38.6). 15 were male and 11 female. In four patients gender was not reported. The ratio of Myocardial Infarction to Ischemic stroke was 12.28 for the hemophilias, 7.83 for vW Disease and 2.75 for the Rare Bleeding Disorders. Risk factors were present in most patients, replacement therapy and old age being the most frequent. CONCLUSIONS:The differences in the prevalence of ischemic stroke vs coronary arterial disease seen in patient with congenital bleeding disorders indicate that clotting defects assure an uneven protection from atherothrombosis. Since the mechanisms underlying these differences are unknown, they represent a field of potential future investigation.

Background True essential thrombocythemia (ET) may carry one of the known driver mutations (JAK2, MPL and CALR) or none of them [in triple-negative (3NEG) cases]. The patients' mutational status seems to delineate the clinical manifestations of ET.Materials and methods We report the data of 183 patients diagnosed with ET strictly according to the WHO 2008 criteria and with a full molecular diagnosis, including the following: 114 patients (62.3%) with JAK2V617F; 25 (13.7%) with CALR type 1 and 19 (10.4%) with CALR type 2; 3 (1.6%) with MPL; 22 (12%) who were 3NEG. Thrombotic risk was assessed by means of the IPSET-thrombosis score (IPSET-T).Results CALR and 3NEG patients had lower haemoglobin levels and leucocyte count than JAK2 patients. CALR patients, and those with type 2 in particular, had higher mean platelet counts and had extreme thrombocytosis more often than any of the other groups. Based on their IPSET-T stratification, 3NEG- and CALR-mutated patients belonged more frequently to the low-risk group and had a significant more favourable thrombosis-free survival rate than those with JAK2 mutation.Conclusion These findings indicate that the three different molecular markers have a significant impact on the clinical course of true ET, giving rise to different phenotypes of the same disease.

Myeloproliferative neoplasms (MPN) are a group of stem cell disorders predominantly occurring in elderly,1 whereas children are affected at much lower frequencies.2 Therefore, less is known about the mutational spectrum and the biology of childhood MPN.3, 4 Lower incidence of JAK2-V617F has been reported in childhood essential thrombocythemia (ET) and polycythemia vera (PV),5, 6 and in recent studies fewer CALR mutations were found in children with ET.7, 8, 9, 10