1 case of red blood cell hyperactivity positive for CALR gene mutation

!----'s CALR gene mutation is commonly found in patients with primary platelet growth (ET) and primary bone marrow fibrosis (PMF) in my-eloproliferative tumors (my-eloproliferative neoplasms, MPN), and is rarely reported in patients with true erythropoietin (PV)? I admitted 1 case of erythrocytic disease patients, bone marrow gene test for the CALR gene mutation positive, is reported as follows, and related literature review?1 case data patients, male, 38 years old? October 2016 due to "dizziness? Physical examination found hemoglobin high 1 week "admission to hospital?" Self-confessed past medical examination has found that hemoglobin slightly high, not concerned, no symptoms of discomfort? 1 week ago began to appear mild dizziness, come to our hospital medical check-up, blood routine: WBC 5.90 x 10 9/L, GR 50.3%, RBC 5.96 x 1012/L, Hb 189g/L, HCT 57%, PLT 246 x 10 9/L? Previous history of chronic globulin nephritis 15 years, traditional Chinese medicine treatment, urine routine: latent blood (plus), egg white (?)? Has a history of hypertension for nearly 10 years, up to 150/100 mmHg (1mmHg x 0.133kPa), oral antihypertensive drug control in the normal range? After admission to the hospital to check liver and kidney skills? Blood sugar is normal? Red-fine cytosin 10.6 mIU/ml? line bone marrow puncture examination, bone marrow like: bone marrow hyperplasia is significantly active; G- 36%, E-49%, G:E s 0.73:1.00? Granulal hyperplasia is active, the morphology is not significantly unusual; red blood cell line hyperplasia is significantly active, accounting for 49% of nuclear cells, mainly in mid-to-late young red blood cells, the morphology is not significantly abnormal; lymphocytes? Single nuclear cells are roughly normal; a total of 89 macronuclear cells, classified 20, of which 12 granulocytes, 8 platelets, platelets easy to see? Bone marrow biopsy: the slice has the growth of nuclear cells reduced, can see a small number of particles? Red and other cells scattered in the distribution, less hematopoietic tissue, increased adipose tissue? What's not seen by the giant nuclear cells? Adipose tissue accounted for 75VoL%? The matrix bleeding was obvious, the matrix edema was obvious? Fiber-free cell hyperplies? Features: (1) bone marrow has nuclear cell growth reduction, hematopoietic tissue accounted for 20VoL, adipose tissue accounted for 75VoL %;(2) visible small amount? Red and other cells scattered in the distribution, macronuclear cells do not see; (3) the matrix blood is obvious, the matrix edema is obvious, no fibroblast hyperpluse? Genetic Test Results: CALR Gene No9 Exon Mutation Detection: Wrong-meaning mutation, mutation site: c.1142A sgt;C (p.E381A)? MPL gene No mutation found on the 10th exon? JAK2 gene V617F mutant negative? BCR/ABL Gene P190? P210 protein is negative? Combined with the above medical history? Blood routine? A bone marrow like? Gene mutation, diagnosed as MPN (CALR gene mutation positive)? Patients do not agree with oral hydroxyrea and interferon treatment, intermittent blood treatment, blood every 3 months, each 300 to 400 ml, blood after blood review hemoglobin can be reduced to 170 to 175g/L, but 3 to 4 weeks later again rise? October 21, 2017 blood routine: 7.WBC 10 x 10 9/L, GR 54.6%, RBC 6.26 x 1012/L, Hb 201g/L, HCT 61.9%, PLT 298 x 10 9/L? Blood creatininininininininine 128 ?mol/L, blood urea 8.76mmol/L? has not yet agreed to oral hydroxyrea chemotherapy, followed by regular blood release? Medical treatment discharge?2 Discussion 2008, WHO officially will PV?ET? PMF is classified as BCR-ABL fusion base due to vulva myelin growth tumor (CMPN) (CMPN) (1)? Since 2005, a number of research centers abroad have gradually discovered the existence of JAK2-V617F in CMPN? MPL - W515? JAK2 - exon12 and other fusion gene mutation sites, JAK2 - V617F in about 90% PV and 50% Of ET/PMF, JAK2 - exon12 in 5% PV, MPL-- W515 exists in 3% to 5% of ET/PMF patients , but still has 5% PV and 30% to 40% of ET/PMF for JAK2 (-) and MPL (-), is it difficult to diagnose? In 2013, Austrian scientist Klampfl et alfirst reported that the application of genome-wide sequencing technology in JAK2 and MPL wild ET/PMF patients found calcium net protein gene (CALR-based) mutation? The CALR gene is located on chromosome 19 and consists of nine exons and eight inclusions? At present, 55 kinds of CALR gene mutants have been found, the site is located in the no9 exon, the mutation type is the transcoding mutation, the most common is the type I variant (L367fs x 46) and type II variant (K385fs x 47), about 80% of the 4?? Has a study of CALR target genetic testing in non-MPN populations found in healthy individual control groups? Lymphatic tumor? No CALR gene mutation was found in acute leukemia and solid tumors( 5)? Is the CALR gene mutation independent from the JAK2 and MPL mutations? Studies have found that the calR gene mutation induced CMPN may be: (1) CALR gene mutation may play a similar function to the JAK2-V617F gene mutation in signaling and activation of the STAT signaling pathway; Several clinical studies have shown that the CALR gene mutation is mainly present in ET/PMF patients with JAK2 (-)/MPL(-) Tef-feri etal 4 used the full exon sequencing method to detect 896 cases of CMPN (382 PV?311 cases of ET?203 cases of PMF), the results show that the CALR gene mutation is not seen in PV, in JAK2 (-))) / MPL () ET/PMF CALR gene mutation rate of 70% to 84%? In JAK2/MPL double-negative ET and PMF patients, 60% to 88% expressED CALR gene mutations? Ojeda et al6 tested 439 Cases of BCR/ABL (-) MPN patients (176 PV?214 cases of ET and 49 pmF) of JAK2 - V617F? JAK2 - exon12? MPL-W515L/K and CALR mutations, the results show that patients with JAK2-V617F (plus) accounted for 74.9%, CALR patients accounted for 12.3%, MPL (plus) patients accounted for 2.1%, 10.7% triple negative? 9 CALR mutations found in ET? In ET, calR patients and low age compared to JAK2-V617F and triple negative patients? High platelets related? Rumi et al(7) collated data on 1,235 MPN patients, 468 cases of JAK2 (-) PV?717 cases of ET (466 cases JAK2()ET, 176 cases CALR (?) ET, 7 5 cases of JAK2 (- / MPL (- / CALR (- ) ET?22 cases JAK2 - exon12 ()PV?28 cases of MPL (-) ET, a total of 23 CALR mutations were found? CALR (-)ET patients and JAK2 (plus)ET patients? A comparison of JAK2 (-) PV patients found that CALR (plus) ET patients occurred more in men, the age of onset was lower than in jak2 (plus) ET patients, the number of hemoglobin and white blood cells was also lower, and the number of platelets and erythropoietin levels were higher? Compared to patients with the JAK2-V617F gene mutation, the CALR gene mutation and the younger median age? Lower white blood cell and hemoglobin levels? Higher platelet counts and rare platelet increases have a correlation? Median lifetimes were 21.4 years and 11.0 years for PATIENTs with CALR (plus) PMF and JAK2 (plus) PMF patients, respectively0.001), CALR (-)ET patients have a 10-year survival rate of 96.9%, the incidence of leukemia event CALR (-) ET patients is lower than other types of MPN, and some JAK2 (-) ET patients will gradually develop to PV, CALR (plus) ET patients have no such phenomenon? The incidence of 10-year cumulative thrombosis in patients with CALR (plus) ET and JAK2 (plus)ET patients was 11.0% and 21.0% respectively ( P - 0.003)? In the Asian population, the genetic testresults of MPN patients were similar? Kim et al(8) tested 199 MPN patients (54 pmF?79 cases of ET?58 cases OF PV? 8 cases of MPN-u) of the base cause CALR? JAK2 and MPL?? showed CALR mutations in 25 patients (12.6%), MPN-u 37.5%, ET 17.7%, PMF 14.8%; Yu Mengyun et al(2017) used direct sequencing to detect 1,648 Ph-negative MPN patients (508 PV?)1 049 cases ET?91 pmF), PV 92.7% JAK2-V617F (-), 1.7% JAK2 - exon12 (?); (- 12.6 percent CALR, 0.9% MPL (plus), PMF 81.3% JAK2-V617F (plus), 12.1% CALR (plus), 1.1% MPL (plus)? CALR sudden change in JAK2 (-)/MPL(-) in the ET and PMF detection rate is higher, 59.7% and 68.8% respectively? Who revised the MPN diagnostic standard in 2014, the main diagnostic criteria for PV are: (1) Hb?gt;165g/L (male)? Hb?gt;160g/L (female), or HCT?gt; 49% (male)? 48% (female) ;(2) bone marrow biopsy shows three-line hyperplaging with polymorphic macronuclear cells; (3) has JAK2 mutations? In addition, PV bone marrow biopsies in multiple blood periods often show bone marrow red lineage? The hypergrowth of the macronuclear system and the granule system is extremely active, a large number of red precellular cells and macronuclear cells proliferate, even if the degree of bone marrow hyperplation is normal, macronuclear cells are also significantly increased group aggregation distribution; The main diagnostic criteria for ET include: (1) PLT(2) Macronuclear cells are highly hyperplasia, mainly large mature macronuclear cells; (3) can not meet PV? Chronic granulocytic leukemia (BCR-ABL fusion gene negative)? WHO diagnostic criteria for PMF?bone marrow hyperplasia syndrome (no granulation and red disease) or other myelin tumors; MPL or CALR mutation? The main diagnostic criteria for PMF include: (1) hypernuclear cell hyperplasia and heterogeneous macronuclear cells, often accompanied by mesh fiber or collagen fiber, or no significant mesh fiber increase (MF - 1), macronucleocellular changes must be accompanied by the growth of nuclear cells in the bone marrow, and granule cell proliferation and red line cell proliferation is often reduced (i.epre-fibrosis cell phase) ;(2) can not be satisfied with PV? Chronic granulocytic leukemia (BCR-ABL fusion gene negative)? Osteomy myelomyal hyperplasia syndrome (no granulator line and red line diseased hematopoietic) or other myelin tumors of the WHO diagnostic criteria; CALR or MPL mutation? Increased blood cells outside the patient?? Hemoglobin rise as the main performance, although the bone marrow like red blood cell line hyperplinter significantly active, accounting for 49% of nuclear cells, but the bone marrow macronucleosis is not active, anti-red cell progenitor level is not high, bone marrow biopsy pathology shows that there is a reduction in nucleocellular growth, hematopoietic tissue accounted for 20VoL, adipose tissue accounted for 75VoL, these are not in line with the change of PV? Therefore, it can not be diagnosed as PV? But the patient's various test results are not consistent with the eT and PMF diagnosis, therefore can not determine which specific type of MPN the patient belongs to? Consider that the patient may also be an early stage of a certain MPN, red system replacement growth, but there is no classic bone marrow morphology and pathological changes, need to dynamically observe the changes in bone marrow and bone marrow and biopsy, in order to further diagnose? At present, the patient has no obvious symptoms of discomfort, blood pressure control is good, dynamic observation? A tip of the reference?