Janus kinase 2 V617F mutation is detectable in spleen of patients with chronic myeloproliferative diseases suggesting a malignant nature of splenic extramedullary hematopoiesis

Konoplev, Sergej; Hsieh, Pin‐Pen; Chang, Chung Che; Medeiros, L. Jeffrey; Lin, Pei

doi:10.1016/j.humpath.2007.04.004

Cited by 21 publications

(17 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3-5 There, the bone marrow derived cells undergo sustained malignant multilineage hematopoiesis resulting in progressive splenomegaly. Studies based on the identification of loss of heterozygosity 6 and presence of JAK2 V617 mutation 7, 8 have provided evidence that splenic extramedullary hematopoiesis in myeloproliferative neoplasms is clonal, supporting the hypothesis that hematopoietic cells causing the splenic proliferation are derived from the transformed bone marrow clones. To further emphasize the neoplastic nature of splenic extramedullary hematopoiesis in myeloproliferative neoplasms and to distinguish it from reactive extramedullary hematopoiesis, O’Malley et al have proposed to use the term, “splenic hematopoietic proliferation” in this disease context.…”

Section: Introductionmentioning

confidence: 86%

Splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms: heterogeneous morphology and cytological composition

et al. 2012

View full text Add to dashboard Cite

We studied 24 spleens with extramedullary hematopoietic proliferation, a key feature of advanced stage Philadelphia chromosome-negative myeloproliferative neoplasms, obtained from 24 patients (14 primary myelofibrosis, 7 polycythemia vera, and 3 unclassifiable). Hematoxylin and eosin, reticulin and trichrome stains and immunohistochemical stains for myeloperoxidase, glycophorin-C, CD42b, CD34, CD117, CD8, nerve growth factor receptor and smooth muscle actin were evaluated. Clinical information was correlated with the morphologic findings. Three distinct histological patterns of extramedullary hematopoietic proliferation were recognized: diffuse (12), nodular (5), and mixed-nodular and diffuse (7). The preponderant lineage was granulocytic in diffuse, trilineage in nodular and erythroid in mixed extramedullary hematopoietic proliferation. Erythropoiesis was largely intravascular, granulopoiesis was within the splenic cords and megakaryopoiesis was observed in both locations. The stromal changes paralleled the histological pattern with preservation of the splenic stromal and vascular architecture in the diffuse areas as opposed to areas of nodular extramedullary hematopoietic proliferation. The morphologic features of splenic extramedullary hematopoietic proliferation did not correlate with specific subtypes of myeloproliferative neoplasms. The mean duration of follow-up from initial diagnosis was 80 months. Fifteen of the 24 patients died of disease: 8 of 12 (67%) with diffuse, 2 of 5 (40%) with nodular and 5 of 7 (71%) with mixed growth patterns. The mean duration from diagnosis to splenectomy was shorter in patients with diffuse (83 months) as compared to those with nodular extramedullary hematopoietic proliferation (127 months). Our study demonstrates that splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms shows distinct histological patterns that do not correlate with disease subtypes but appear to suggest a trend between the histologic patterns and clinical behavior. These results suggest a different biology of the disease in the nodular and diffuse extramedullary hematopoietic proliferation groups.

show abstract

Section: Introductionmentioning

confidence: 86%

Splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms: heterogeneous morphology and cytological composition

et al. 2012

View full text Add to dashboard Cite

show abstract

“…EMH in adults is typically seen in patients with myeloproliferative neoplasms (MPNs) but its association also with other conditions, including thalassemia, has long been recognized 1 . In both MPN and non-MPN settings, the liver and spleen are the two most frequent sites of EMH and it has been hypothesized that circulating hematopoietic cell filtration (entrapment), possibly via endothelial cell expressed ligands, such as chemokine ligand 12, rather than splenic stroma account for the particular phenomenon 2 – 4 ; the concordant detection of MPN-specific mutations, such as JAK2 V617F, and specific cytogenetic abnormalities in both bone marrow and splenic tissue of affected patients, supports this contention 5 , 6 .…”

mentioning

confidence: 98%

Extramedullary hematopoiesis in the absence of myeloproliferative neoplasm: Mayo Clinic case series of 309 patients

Fan

Lavu

Hanson

et al. 2018

Blood Cancer Journal

View full text Add to dashboard Cite

“…The liver findings after splenectomy also reflect the end stage of a hematopoietic shift from the biopsy‐proven fibrotic medullary cavity to the liver, where the presence of the JAK2 mutation provides molecular evidence of a similar shift of the myeloproliferative clone to this site of embryonic hematopoiesis. Thereby, the findings combine components of existing theories of EMH discussed in the context of PV2 and myelofibrosis 3…”

mentioning

confidence: 53%

Massive Hepatomegaly and Involvement by Janus Kinase 2–Positive Myeloproliferative Neoplasm

2010

View full text Add to dashboard Cite

Janus kinase 2 V617F mutation is detectable in spleen of patients with chronic myeloproliferative diseases suggesting a malignant nature of splenic extramedullary hematopoiesis

Cited by 21 publications

References 15 publications

Splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms: heterogeneous morphology and cytological composition

Splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms: heterogeneous morphology and cytological composition

Extramedullary hematopoiesis in the absence of myeloproliferative neoplasm: Mayo Clinic case series of 309 patients

Massive Hepatomegaly and Involvement by Janus Kinase 2–Positive Myeloproliferative Neoplasm

Contact Info

Product

Resources

About