Quantification of IGF‐1 receptor is useful in the differential diagnosis of essential thrombocytosis from reactive thrombocytosis

Abstract

The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia lists the criteria for diagnosing essential thrombocythemia (ET) as (a) platelet count more than 450 × 10 9 /L; (b) bone marrow biopsy showing proliferation mainly of the megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei; no significant increase or left shift in neutrophil granulopoiesis or erythropoiesis; and very rarely a minor (grade 1) increase in reticulin fiber; (c) not meeting WHO criteria for CML, PV, PMF, myelodysplastic syndromes, or other myeloid neoplasms; and (d) the presence of JAK2, CALR, or MPL mutation. The minor criteria include the presence of a clonal marker or the absence of evidence of reactive thrombocytosis. 1Among these criteria, the most reliable criteria for diagnosing ET are the "presence of JAK2, CALR, or MPL mutation". These mutually exclusive "driver" mutations have respective incidences of 55%, 25%, and 3%, and the remaining of 17% are so-called triplenegative ET. 2 These 17% of cases will need other criteria to make a definite diagnosis as ET. The bone marrow criterion is helpful in Abstract Background: To make a definite diagnosis of essential thrombocytosis (ET) from reactive thrombocytosis (RT), the most reliable criteria are the presence of driver mutations, namely JAK2, CALR, or MPL gene mutations. In the absence of these driver mutations, so-called triple-negative ET, the differential diagnosis could be difficult.Although bone marrow biopsy could be helpful, it may be difficult in some cases, to do gene sequence analysis to identify other clonal marker gene mutations than the driver mutations, as only very few were found. Methods: IGF-1R quantification by flow cytometry in mononuclear cells (MNC) fromperipheral blood was performed in 33 patients with ET (untreated or off treatment with hydroxyurea), 28 patients with RT, and 16 normal volunteer controls. Results:We found IGF-1R levels were significantly elevated in ET patients compared to RT patients or controls. A cutoff value of 253 was chosen from the logistic regression to predict each patient's group, a value ≥253 meant that a patient belonged to the ET group (sensitivity 96.4% and specificity 68.6%). Conclusion:We suggest that adding quantification of IGF-1R in blood MNC by flow cytometry is useful in differentiating ET from RT. K E Y W O R D Sessential thrombocytosis (ET), insulin-like receptor growth factor-1 receptor (IGF-1R), reactive thrombocytosis (RT) | 577 WANG et Al.

Designing a Scoring System for Differential Diagnosis From Reactive Thrombocytosis and Essential Thrombocytosis

“…Wang et al attempted to use amount of IGF-1 receptor in the differential diagnosis. The levels of IGF-1R were significantly elevated in ET groups compared to in RT groups or controls ( 18 ). Ryningen et al reported that RT or thrombocytopenia will increase platelet turnover, thus increasing the circulating number of reticulated platelets in myeloproliferative disorders.…”