JAK2
 ,
 CALR
 ,
 MPL
 and
 ASXL1
 mutational status correlates with distinct histological features in Philadelphia chromosome-negative myeloproliferative neoplasms

Wong, Waihay J.; Pinkus, Geraldine S.; Breyfogle, Lawrence J.; Mullally, Ann; Pozdnyakova, Olga

doi:10.3324/haematol.2017.178988

Cited by 15 publications

(19 citation statements)

References 15 publications

(6 reference statements)

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“…We previously demonstrated that the mutational profiles of PMF, ET, and PV correlate with histomorphologic characteristics in a cohort of Ph-negative MPN patients [4]. In this study, we expand this cohort of PMF, ET, and PV patients to characterize levels of inflammatory gene expression in the bone marrow.…”

Section: Introductionmentioning

confidence: 92%

Gene expression profiling distinguishes prefibrotic from overtly fibrotic myeloproliferative neoplasms and identifies disease subsets with distinct inflammatory signatures

et al. 2019

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The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) share similar molecular characteristics in that they frequently harbor hotspot mutations in JAK2 , CALR or MPL , leading to activated JAK/STAT signaling. However, these MPN have distinct symptoms, morphology, and natural histories, including different tendencies to progress to fibrosis. Although the role of inflammation in tissue fibrosis is well recognized, inflammatory gene expression in bone marrows involved by MPN has been understudied. We analyzed the expression of inflammatory genes by directly measuring RNA transcript abundance in bone marrow biopsies of 108 MPN patients. Unsupervised analyses identified gene expression patterns that distinguish prefibrotic (grade 1–2) MPN from overtly fibrotic (grade 2–3) MPN with high sensitivity and specificity in two independent cohorts. Furthermore, prefibrotic and overtly fibrotic MPN are separable into subsets with different activities in biological pathways linked to inflammation, including cytokines, chemokines, interferon response, and toll-like receptor signaling. In conclusion, this study demonstrates that MPN with overt fibrosis is associated with significant inflammatory gene upregulation in the bone marrow, revealing potential roles for multiple pro-inflammatory signaling networks in the development of myelofibrosis and suggesting potential therapeutic mechanisms to alleviate this process in the bone marrow microenvironment.

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Section: Introductionmentioning

confidence: 92%

Gene expression profiling distinguishes prefibrotic from overtly fibrotic myeloproliferative neoplasms and identifies disease subsets with distinct inflammatory signatures

et al. 2019

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“…In contrast, early (prefibrotic) PMF shows little to no reticulin fibrosis and subtle morphologic findings which mimic those of prefibrotic PV and ET. In our experience, tight megakaryocyte clustering and atypical “bulbous” morphology remain the most specific morphologic features in diagnosing prefibrotic PMF (Figure C).…”

Section: Bcr‐abl1‐negative Mpnmentioning

confidence: 67%

Myeloproliferative neoplasms: Diagnostic workup of the cythemic patient

Wong

Pozdnyakova

2019

Int J Lab Hematology

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Elevated peripheral blood (PB) cell counts, such as leukocytosis, thrombocytosis, and polycythemia, are often the presenting symptom in patients with myeloproliferative neoplasms (MPN). Because cythemias are nonspecific and may reflect either a reactive or neoplastic process, diagnostic workup of these patients is complicated and requires integration of numerous diagnostic modalities. Careful morphologic evaluation of the PB smear may provide insights into the underlying cause of the abnormal counts (such as the presence of teardrop erythrocytes in myelofibrosis or granulocytic dysplasia with left shift in atypical chronic myeloid leukemia). However, these morphologic findings need to be interpreted in concert with clinical findings and other laboratory results. In recent years, there has been a wealth of new genetic data in the field of MPN and many recurrent mutations have been identified, especially in cases lacking Philadelphia chromosome. Many of these genes impact the diagnosis and/or prognosis. Although certain mutations are preferentially enriched in specific MPN types, none of these mutations are disease defining; therefore, a thorough workup should always include a bone marrow biopsy for morphologic evaluation and diagnosis. This review will describe a comprehensive approach to the diagnosis of various MPN, with an emphasis on the diagnostic and prognostic implications of recurrent mutations in MPN.

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“…Previous studies have hypothesized that JAK2 V617F , CALR, and MPL are the drivers of MPN pathogenesis [10,[30][31][32][33]. Since JAK2 V617F is present in both PV and ET patients, we compared their blood parameters.…”

Section: Discussionmentioning

confidence: 99%

The effects of mutational profiles on phenotypic presentation of myeloproliferative neoplasm subtypes in Bosnia: 18 year follow-up

Kurtovic-Kozaric

Islamagić

Komic

et al. 2019

Bosn J of Basic Med Sci

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The identification of mutually exclusive somatic mutations shared among myeloproliferative neoplasm (MPN) subtypes has provided a powerful tool for studying disease evolution. Clinical features, gene mutations, and survival over 18 years were analyzed in MPN patients. One hundred thirty-eight MPN patients were subcategorized according to MPN subtypes: essential thrombocythemia (ET, n = 41), polycythemia vera (PV, n = 56), primary myelofibrosis (PMF, n = 10), and MPN unclassified (MPN-U, n = 31). Patient characteristics included clinical parameters, overall survival, and mutational status of the JAK2, CALR, and MPL genes. We compared hematologic and clinical features of JAK2V617F-ET vs. CALR-mutated ET vs. JAK2V617F-PV patients. JAK2V617F-patients had higher values of erythrocytes, hemoglobin, and hematocrit compared to CALR-mutated patients (p < 0.05). The mutant allele burden in JAK2V617F-PV and JAK2V617F-ET patients directly correlated with erythrocyte, hemoglobin, and hematocrit values, but it inversely correlated with platelet count. Thus, mutant allele burden was an indicator of the clinical phenotype in JAK2V617F-MPN patients. OS was not affected by the mutational status. In general, mutated JAK2, CALR, and MPL genes left specific hematological signatures.

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JAK2 , CALR , MPL and ASXL1 mutational status correlates with distinct histological features in Philadelphia chromosome-negative myeloproliferative neoplasms

Cited by 15 publications

References 15 publications

Gene expression profiling distinguishes prefibrotic from overtly fibrotic myeloproliferative neoplasms and identifies disease subsets with distinct inflammatory signatures

Gene expression profiling distinguishes prefibrotic from overtly fibrotic myeloproliferative neoplasms and identifies disease subsets with distinct inflammatory signatures

Myeloproliferative neoplasms: Diagnostic workup of the cythemic patient

The effects of mutational profiles on phenotypic presentation of myeloproliferative neoplasm subtypes in Bosnia: 18 year follow-up

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