Pathogenesis of myeloproliferative neoplasms

Skoda, Radek C.; Duek, Adrian; Grisouard, Jean

doi:10.1016/j.exphem.2015.06.007

Cited by 100 publications

(93 citation statements)

References 133 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Philadelphia-chromosome or BCR-ABL1 negative myeloproliferative neoplasms (MPNs) represented by polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are characterized by increased proliferation of erythroid, megakaryocytic, or granulocytic cells [1]. Major progress has been recently made in understanding the molecular pathogenesis of MPNs.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations

et al. 2016

View full text Add to dashboard Cite

Increased angiogenesis in BCR-ABL1 negative myeloproliferative neoplasms (MPNs) has been recognized, but its connection with clinical and molecular markers needs to be defined. The aims of study were to (1) assess bone marrow (BM) angiogenesis measured by microvessel density (MVD) using CD34 and CD105 antibodies; (2) analyze correlation of MVD with plasma angiogenic factors including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8; (3) examine the association of MVD with clinicopathological and molecular markers. We examined 90 de novo MPN patients (30 polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET)) and 10 age-matched controls. MVD was analyzed by immunohistochemistry "hot spot" method, angiogenic factors by immunoassay and JAK2V617F, and CALR mutations by DNA sequencing and allelic PCR. MVD was significantly increased in MPNs compared to controls (PMF> PV > ET). Correlation between MVD and plasma angiogenic factors was found in MPNs. MVD was significantly increased in patients with JAK2V617F mutation and correlated with JAK2 mutant allele burden (CD34-MVD: ρ = 0.491, p < 0.001; CD105-MVD: ρ = 0.276, p = 0.02) but not with CALR mutation. MVD correlated with leukocyte count, serum lactate dehydrogenase, hepatomegaly, and splenomegaly. BM fibrosis was significantly associated with CD34-MVD, CD105-MVD, interleukin-8, and JAK2 mutant allele burden. JAK2 homozygote status had positive predictive value (100%) for BM fibrosis. Patients with prefibrotic PMF had significantly higher MVD than patients with ET, and we could recommend MVD to be additional histopathological marker to distinguish these two entities. This study also highlights the strong correlation of MVD with plasma angiogenic factors, JAK2 mutant allele burden, and BM fibrosis in MPNs.

show abstract

Section: Introductionmentioning

confidence: 99%

Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations

et al. 2016

View full text Add to dashboard Cite

show abstract

“…1 CALR mutations were discovered in 50% to 80% of patients with JAK2 and MPL wild-type essential thrombocythemia (ET) and primary myelofibrosis (PMF), representing 20% to 35% of all patients with ET and PMF. This discovery was a landmark finding in understanding the pathogenesis of JAK2-and MPL-negative MPNs.…”

mentioning

confidence: 99%

CAL2 Immunohistochemical Staining Accurately IdentifiesCALRMutations in Myeloproliferative Neoplasms

et al. 2016

View full text Add to dashboard Cite

Objectives: Mutations in CALR (calreticulin) have been discovered in 50% to 80% of JAK2 (Janus kinase 2) and MPL (myeloproliferative leukemia protein) wild-type patients with Philadelphia-negative myeloproliferative neoplasm (MPNs). We evaluate the performance of a monoclonal antibody for immunohistochemical detection of CALR mutations.Methods: A computerized archival search was performed for cases of non-chronic myeloid leukemia (CML) MPNs with available CALR and JAK2 V617F mutational analysis data. Bone marrow biopsy specimens were stained with monoclonal antibody CAL2, and the percentage of stained megakaryocytes was calculated. In select cases, double immunofluorescence staining was done with CAL2 and each of the following: CD61, myeloperoxidase, CD34, and glycophorin A.

show abstract

“…However, variants in other genetic regions are also common, including CALR exon 9 (;25% ET, ;35% PMF), MPL exon 10 (;4% PMF, ;1% ET), and JAK2 exon 12 (;4% PV). [184][185][186][187][188] All those aberrations are part of diagnostic criteria in MPN and represent attractive targets for MRD monitoring. 189 For tracking of JAK2 V617F, qPCR currently represents the most reliable and sensitive method (;0.01%) and is widely used in clinical trials and routine laboratories to assess patient outcomes.…”

Section: Chronic Myeloid Leukemiamentioning

confidence: 99%

“…183,[195][196][197][198] HTS-based approaches are not broadly established yet for routine MPN molecular diagnostics, but their capacity to simultaneously cover multiple genetic variants make them a promising tool for monitoring the genetic complexity of MPN. 184,185,197 Abdelhamid et al demonstrated in a proof-of-principle study robust detection of JAK2 V617F in PB by HTS with high concordance to qPCR, even at low AFs. 199 Lundberg et al applied a targeted HTS panel (104 genes) to serial blood samples and showed that the number of emergent mutations over time was low, characterizing these diseases as genetically stable.…”

Section: Chronic Myeloid Leukemiamentioning

confidence: 99%

High-throughput sequencing for noninvasive disease detection in hematologic malignancies

Scherer

Kurtz

Diehn

et al. 2017

Blood

View full text Add to dashboard Cite

Noninvasive monitoring of minimal residual disease (MRD) has led to significant advances in personalized management of patients with hematologic malignancies. Improved therapeutic options and prolonged survival have further increased the need for sensitive tumor assessment that can inform treatment decisions and patient outcomes. At diagnosis or relapse of most hematologic neoplasms, malignant cells are often easily accessible in the blood as circulating tumor cells (CTCs), making them ideal targets to noninvasively profile the molecular features of each patient. In other cancer types, CTCs are generally rare and noninvasive molecular detection relies on circulating tumor DNA (ctDNA) shed from tumor deposits into circulation. The ability to precisely detect and quantify CTCs and ctDNA could minimize invasive procedures and improve prediction of clinical outcomes. Technical advances in MRD detection methods in recent years have led to reduced costs and increased sensitivity, specificity, and applicability. Among currently available tests, high-throughput sequencing (HTS)–based approaches are increasingly attractive for noninvasive molecular testing. HTS-based methods can simultaneously identify multiple genetic markers with high sensitivity and specificity without individual optimization. In this review, we present an overview of techniques used for noninvasive molecular disease detection in selected myeloid and lymphoid neoplasms, with a focus on the current and future role of HTS-based assays.

show abstract

Pathogenesis of myeloproliferative neoplasms

Cited by 100 publications

References 133 publications

Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations

Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations

CAL2 Immunohistochemical Staining Accurately IdentifiesCALRMutations in Myeloproliferative Neoplasms

High-throughput sequencing for noninvasive disease detection in hematologic malignancies

Contact Info

Product

Resources

About