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Current Hematologic Malignancy Reports Feb 2022Myeloproliferative neoplasms (MPN) are a heterogeneous group of hematopoietic stem cell neoplasms comprising of polycythemia vera (PV), essential thrombocythemia (ET),... (Review)
Review
PURPOSE OF REVIEW
Myeloproliferative neoplasms (MPN) are a heterogeneous group of hematopoietic stem cell neoplasms comprising of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) that share driver mutations (JAK2/CALR/MPL) resulting in constitutive activation of JAK/STAT and other signaling pathways. Patients with MPN have shortened survival and an inherent risk for leukemic evolution. Prognostically relevant clinical and genetic parameters have been incorporated into mutation-enhanced scoring systems (MIPSS70-plus version 2.0, MIPSS-ET/PV). In the current review, we describe clinical and pathological features along with prognostic significance of MPN with monocytosis.
RECENT FINDINGS
Monocytosis, defined by an absolute monocyte count (AMC) ≥ 1 × 10 /L, is a typical manifestation of chronic myelomonocytic leukemia (CMML) but is also associated with 21% and 17% of PV and PMF patients, respectively. Recent studies on the subject have reported that MPN patients with monocytosis are older and present with concomitant leukocytosis. In regard to PV, patients with monocytosis harbor unfavorable cytogenetic abnormalities including +8, 7/7q, i(17q), 5/5q-,12p-, inv(3), or 11q23 rearrangement and SRSF2 mutations, whereas PMF patients with monocytosis had significant thrombocytopenia, higher circulating blasts, higher symptom burden, and ASXL1 mutations. Moreover, presence of monocytosis predicted inferior survival in both PV and PMF. Monocytosis in MPN is associated with a distinct clinical and genetic profile and may serve as a marker of aggressive disease biology.
Topics: Humans; Janus Kinase 2; Leukocytosis; Mutation; Myeloproliferative Disorders; Polycythemia Vera; Thrombocythemia, Essential
PubMed: 34773576
DOI: 10.1007/s11899-021-00660-2 -
International Journal of Laboratory... Apr 2018Monocytosis is a common finding that is caused by a wide variety of neoplastic and non-neoplastic conditions. The adequate evaluation of monocytosis involves the... (Review)
Review
Monocytosis is a common finding that is caused by a wide variety of neoplastic and non-neoplastic conditions. The adequate evaluation of monocytosis involves the integration of laboratory data, morphology, clinical findings, and the judicious use of ancillary studies. We review the literature on monocytosis, including the 2017 revised 4th edition of the World Health Organization classification of hematopoietic neoplasms. We present a review of monocytosis with practical guidelines on how to approach both routine and challenging cases.
Topics: Hematologic Neoplasms; Humans; Leukocytosis; Monocytes; Practice Guidelines as Topic
PubMed: 29345409
DOI: 10.1111/ijlh.12776 -
Current Hematologic Malignancy Reports Jun 2021Juvenile myelomonocytic leukemia (JMML) is a rare but severe pediatric neoplasm with hematopoietic stem cell transplant as its only established curative option. The... (Review)
Review
PURPOSE OF REVIEW
Juvenile myelomonocytic leukemia (JMML) is a rare but severe pediatric neoplasm with hematopoietic stem cell transplant as its only established curative option. The development of targeted therapeutics for JMML is being guided by an understanding of the pathobiology of this condition. Here, we review JMML with an emphasis on genetics in order to (i) demonstrate the relationship between JMML genotype and clinical phenotype and (ii) explore potential genetic targets of novel JMML therapies.
RECENT FINDINGS
DNA hypermethylation studies have demonstrated consistently that methylation is related to disease severity. Increasing understanding of methylation in JMML may open the door to novel therapies, such as DNA methyltransferase inhibitors. The PI3K/AKT/MTOR, JAK/STAT, and RAF/MEK/ERK pathways are being investigated as therapeutic targets for JMML. Future therapy for JMML will be driven by an increased understanding of pathobiology. Targeted therapeutic approaches hold potential for improving outcomes in patients with JMML.
Topics: Biomarkers, Tumor; Combined Modality Therapy; Disease Management; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Leukemia, Myelomonocytic, Juvenile; Mutation; Phenotype; Symptom Assessment
PubMed: 33630234
DOI: 10.1007/s11899-021-00611-x -
Blood Advances Jul 2022Monocytosis may occur in numerous inflammatory conditions but is also the defining feature of chronic myelomonocytic leukemia (CMML). Clonal somatic mutations detectable...
Monocytosis may occur in numerous inflammatory conditions but is also the defining feature of chronic myelomonocytic leukemia (CMML). Clonal somatic mutations detectable in CMML may occur with aging in otherwise healthy individuals, so-called "clonal hematopoiesis" (CH). We investigated whether the combination of CH and monocytosis would represent an early developmental stage of CMML. We studied community-dwelling individuals with monocytosis (≥1 × 109/L and ≥10% of leukocytes) in the population-based Lifelines cohort (n = 144 676 adults). The prevalence and spectrum of CH were evaluated for individuals ≥60 years with monocytosis (n = 167 [0.8%]), and control subjects 1:3 matched for age and sex (n = 501). Diagnoses of hematological malignancies were retrieved by linkage to the Netherlands Cancer Registry (NCR). Monocyte counts and the prevalence of monocytosis increased with advancing age. Older individuals with monocytosis more frequently carried CH (50.9% vs 35.5%; P < .001). Monocytosis is associated with enrichment of multiple gene mutations (P = .006) and spliceosome mutations (P = .007) but not isolated mutated DNMT3A, TET2, or ASXL1. Persistent monocytosis over 4 years was observed in 30/102 evaluable individuals and associated with a higher prevalence of CH (63%). Myeloid malignancies, including 1 case of CMML, developed in 4 individuals with monocytosis who all carried CH. In conclusion, monocytosis and CH both occur at an older age and do not necessarily reflect clonal monocytic proliferation. In a fraction of older subjects with monocytosis, CH might constitute early clonal dominance in developing malignant myelomonocytic disease. Mutational spectra deviating from age-related CH require attention.
Topics: Adult; Clonal Hematopoiesis; Humans; Independent Living; Leukemia, Myelomonocytic, Chronic; Leukocytosis; Mutation; Myeloproliferative Disorders
PubMed: 35561316
DOI: 10.1182/bloodadvances.2021006755 -
Current Hematologic Malignancy Reports Jun 2021In this review, we provide a comprehensive and contemporary understanding of malignant monocytosis and provide a framework by which the appropriate diagnosis with... (Review)
Review
PURPOSE OF REVIEW
In this review, we provide a comprehensive and contemporary understanding of malignant monocytosis and provide a framework by which the appropriate diagnosis with malignant monocytosis can be rendered.
RECENT FINDINGS
Increasing data support the use of molecular data to refine the diagnostic approach to persistent monocytosis. The absence of a TET2, SRSF2, or ASXL1 mutation has ≥ 90% negative predictive value for a diagnosis of CMML. These data may also reliably differentiate chronic myelomonocytic leukemia, the malignancy that is most associated with mature monocytosis, from several other diseases that can be associated with typically a lesser degree of monocytosis. These include acute myelomonocytic leukemia, acute myeloid leukemia with monocytic differentiation, myelodysplastic syndromes, and myeloproliferative neoplasms driven by BCR-ABL1, PDGFRA, PDGFRB, or FGFR1 rearrangements or PCM1-JAK2 fusions among other rarer aberrations. The combination of monocyte partitioning with molecular data in patients with persistent monocytosis may increase the predictive power for the ultimate development of CMM but has not been prospectively validated. Many conditions, both benign and malignant, can be associated with an increase in mature circulating monocytes. After reasonably excluding a secondary or reactive monocytosis, there should be a concern for and investigation of malignant monocytosis, which includes hematopathologic review of blood and marrow tissues, flow cytometric analysis, and cytogenetic and molecular studies to arrive at an appropriate diagnosis.
Topics: Age of Onset; Algorithms; Animals; Biomarkers, Tumor; Biopsy; Bone Marrow; Clinical Decision-Making; Disease Management; Disease Susceptibility; Gene Expression Regulation, Leukemic; Humans; Immunohistochemistry; Leukemia, Myeloid; Monocytes; Neoplasms, Second Primary
PubMed: 33890194
DOI: 10.1007/s11899-021-00632-6 -
Current Hematologic Malignancy Reports Jun 2021Monocytosis is a frequently encountered clinical condition that needs appropriate investigation due to a broad range of differential diagnoses. This review is meant to... (Review)
Review
PURPOSE OF REVIEW
Monocytosis is a frequently encountered clinical condition that needs appropriate investigation due to a broad range of differential diagnoses. This review is meant to summarize the latest literature in the diagnostic testing and interpretation and offer a stepwise diagnostic approach for a patient presenting with monocytosis.
RECENT FINDINGS
Basic studies have highlighted the phenotypic and functional heterogeneity in the monocyte compartment. Studies, both translational and clinical, have provided insights into why monocytosis occurs and how to distinguish the different etiologies. Flow cytometry studies have illustrated that monocyte repartitioning can distinguish chronic myelomonocytic leukemia, a prototypical neoplasm with monocytosis from other reactive or neoplastic causes. In summary, we provide an algorithmic approach to the diagnosis of a patient presenting with monocytosis and expect this document to serve as a reference guide for clinicians.
Topics: Biomarkers, Tumor; Bone Marrow; Clonal Evolution; Diagnosis, Differential; Disease Management; Disease Susceptibility; Flow Cytometry; Humans; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic
PubMed: 33880680
DOI: 10.1007/s11899-021-00618-4 -
Annales de Biologie Clinique Oct 2019The discovery of a monocytosis is a frequent phenomenon, requiring confirmation by reading under a microscope by an experimented biologist, to overcome usual cytological... (Review)
Review
The discovery of a monocytosis is a frequent phenomenon, requiring confirmation by reading under a microscope by an experimented biologist, to overcome usual cytological traps such as the presence of hairy cells, promonocytes or monoblasts. In the vast majority of cases the secondary origin is very easily found by the context and/or the presence of a biological inflammatory syndrome. More rarely the diagnosis is directed towards an eosinophilic pathology or an acute leukemia. In other cases, CMML, MPN or MDS with monocytosis may be highlighted. In the absence of any pathognomonic element and the presence of "borderline" forms the differential diagnosis between these 3 entities is not always straightforward, requiring, according to WHO, molecular investigations and elimination of any reactive cause of monocytosis. Although histological, immunohistochemical and phenotypic flow cytometric studies are not currently recommended by WHO, these investigations could be of interest in the evaluation of difficult cases.
Topics: Adult; Age of Onset; Algorithms; Clinical Laboratory Techniques; Diagnosis, Differential; Humans; Leukocyte Count; Monocytes; Myelodysplastic Syndromes
PubMed: 31486402
DOI: 10.1684/abc.2019.1475 -
European Journal of Haematology Apr 2023Monocytosis (≥0.5 × 10 /L in peripheral blood) is the hallmark of chronic myelomonocytic leukaemia (CMML) but may be present in a spectrum of diseases including...
Monocytosis (≥0.5 × 10 /L in peripheral blood) is the hallmark of chronic myelomonocytic leukaemia (CMML) but may be present in a spectrum of diseases including other haematological malignancies. In the primary care sector, monocytosis is a relatively common finding, but its predictive value for haematological malignancy is unknown. We included 663 184 adult primary care patients from the greater Copenhagen area with one or more differential cell counts registered between 2000 and 2016 and followed them in the extensive nationwide Danish health data registers for 3 years after blood sampling. We used logistic regression to model the risk of haematological malignancy and death following monocytosis. Monocytosis was associated with an increased risk of all types of haematological malignancy with the greatest relative risk increase observed in CMML with an OR of 105.22 (95% confidence interval: 38.27-289.30). Sustained monocytosis (at least two requisitions in 3 months) further increased CMML risk, although the diagnosis was still very rare, that is, observed in only 0.1% of these individuals. Outside the haematological setting, the absolute risk of haematological malignancy associated with monocytosis is low and haematological malignancy should mainly be suspected when monocytosis is sustained or the clinical presentation raises suspicion of malignancy.
Topics: Adult; Humans; Monocytes; Leukocytosis; Leukemia, Myelomonocytic, Chronic; Hematologic Neoplasms; Primary Health Care
PubMed: 36479724
DOI: 10.1111/ejh.13911 -
Blood Mar 2024
Topics: Humans; Leukocyte Disorders; Leukocytosis; World Health Organization
PubMed: 38512267
DOI: 10.1182/blood.2023023332 -
Immunological Reviews Nov 2014Monocytes are part of the vertebrate innate immune system. Blood monocytes are produced by bone marrow and splenic progenitors that derive from hematopoietic stem cells... (Review)
Review
Monocytes are part of the vertebrate innate immune system. Blood monocytes are produced by bone marrow and splenic progenitors that derive from hematopoietic stem cells (HSCs). In cardiovascular disease, such as atherosclerosis and myocardial infarction, HSCs proliferate at higher levels that in turn increase production of hematopoietic cells, including monocytes. Once produced in hematopoietic niches, monocytes intravasate blood vessels, circulate, and migrate to sites of inflammation. Monocyte recruitment to atherosclerotic plaque and the ischemic heart depends on various chemokines, such as CCL2, CX3 CL1, and CCL5. Once in tissue, monocytes can differentiate into macrophages and dendritic cells. Macrophages are end effector cells that regulate the steady state and tissue healing, but they can also promote disease. At sites of inflammation, monocytes and macrophages produce inflammatory cytokines, which can exacerbate disease progression. Macrophages can also phagocytose tissue debris and produce pro-healing cytokines. Additionally, macrophages are antigen-presenting cells and can prime T cells. The tissue environment, including cytokines and types of inflammation, instructs macrophage specialization. Understanding monocytosis and its consequences in disease will reveal new therapeutic opportunities without compromising steady state functions.
Topics: Animals; Cardiovascular Diseases; Cell Differentiation; Cell Movement; Hematopoietic Stem Cells; Humans; Inflammation; Leukocytosis; Macrophages; Monocytes; Myeloid Progenitor Cells; Myelopoiesis; Organ Specificity
PubMed: 25319334
DOI: 10.1111/imr.12219