Evidence from molecular genetic and cytogenetic analyses that bone marrow histopathology is reliable in the diagnosis of chronic myeloproliferative disorders

1993 ◽  
Vol 63 (1) ◽  
pp. 199-204 ◽  
Author(s):  
M. Werner ◽  
V. Kaloutsi ◽  
F. Kausche ◽  
T. Buhr ◽  
A. Georgii
Keyword(s):  
Bone Marrow ◽  
Molecular Genetic ◽  
Myeloproliferative Disorders ◽  
Chronic Myeloproliferative Disorders ◽  
Bone Marrow Histopathology ◽  
Cytogenetic Analyses

Relation between JAK2 V617F Mutation and Chronic Myeloproliferative Disorders.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4638-4638
Author(s):  
Zhjian Xiao ◽  
Yue Zhang ◽  
Jianxiang Wang ◽  
Yushu Hao
Keyword(s):  
Bone Marrow ◽  
Jak2 V617f ◽  
Myeloproliferative Disorders ◽  
Hemoglobin Level ◽  
Jak2 V617f Mutation ◽  
Control Group ◽  
Mutation Load ◽  
Chronic Myeloproliferative Disorders ◽  
V617f Mutation ◽  
Secondary Myelofibrosis

Abstract The chronic myeloproliferative disorders (cMPDs) are a group of clonal malignant tumors of the hematological system, and derived from the pluripotential hemopoietic stem cells, manifested as the proliferation of one or more series of cells in the bone marrow as well as the occurrence of excessive mature or naive cells in the peripheral blood. It was reported by several research groups that there was the acquired JAK2 V617F mutation in the majority of the PV patients and in a part of the ET or PMF patients, which provided the new ideas for the investigation of the pathogenesis of BCR/ABL- cMPDs. In the present study, the JAK2 V617F mutation was detected in a larger collection of Chinese cMPD patients, to give a picture of the incidence of JAK2 V617F mutation in the Asian pollutions. A total of 523 patients with the cMPDs, including 278 males and 245 females, were analyzed. Their median age was 50 years old (7 to 83 years old). According to the WHO diagnostic criteria, among the 523 patients were 88 cases of CML at the chronic phase (including 59 males and 29 females with a median age of 40 years old), 25 of CML complicated with myelofibrosis, 116 of PV (64 males and 52 females; a median age of 53; among them were six cases of PV with the secondary myelofibrosis), 153 of ET (63 males and 91 females; a median age of 50; 15 cases of ET with the secondary myelofibrosis), 142 of PMF (71 males and 71 females; a median age of 53.5), four of unclassified CMPD (CMPD-U) (2 males and 2 females; a median age of 60), seven of high eosinophil syndrome (HES) (6 males and 1 female; a median age of 32), and 13 of chronic eosinophilic leukemia (13 males; a median age of 34). In addition, 140 of healthy adults were included in the control group. Allele-specific PCR (ASP) was applied to identify JAK2 V617F mutation, the mutation status was analyzed by PCR-RFLP, and the results were confirmed by sequence analysis. The mutation load was calculated by the ratio of T/G. Then explore the correlation between the allele load and the clinical, hematologic features. To those without JAK2 V617F, MPL W515L mutation was analyzed. JAK2 V617F was detected in 66%(346/523) of all patients (94%(109/116) in PV, 79%(122/153) in ET, 78%(111/142) in PMF, 75%(3/4) in CMPD-U and 14%(1/7) in HES).Majority of patients carried JAK2 V617F mutation were heterozygous, homozygote was found in only 5 cases (4 in PV and 1 in ET). The mutation load in majority patients (71.5%) was low, PV>ET>MF when compared with mutation load (p=0.003). Hemoglobin level was significantly related to high mutation load in PV (p=0.033, r=0.203). Bone marrow megakaryocyte counts were found to be marked increased in ET with high JAK2 V617F loads (P=0.024, r=0.205), and hepatomegaly in PMF was also significiently associated with high JAK2 V617F mution load (p=0.003, 0.001)(p=0.001, r=0.315). Oue data showed that Majority of cMPD patients, especialy with PV, carried JAK2 V617F mutation, but JAK2 V617F was absent in CML; 98% of JAK2 V617F mutation occurs in a heterozygous status, only 4 patients with PV and 1 with ET were homozygouse.; PV> ET> MF when compared with mutation load. High JAK2 V617F loads were found to be significantly associated with higher hemoglobin level in PV and higher bone marrow megakaryocyte counts in ET; The correlation between hepatomegaly and JAK2 V617F mutation load were also found in PMF.

Dynamics of Telomere Length and Telomerase Activity in Ph1-Negative Chronic Myeloproliferative Disorders

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2789-2789
Author(s):  
Ioanna Bazdiara ◽  
Despina Pantelidou ◽  
Athanasios Anastasiadis ◽  
Vassilios Papadopoulos ◽  
Dimitrios Margaritis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Telomere Length ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Hematopoietic Cells ◽  
Myeloproliferative Disorders ◽  
Telomerase Activity ◽  
Secondary Leukemia ◽  
Chronic Myeloproliferative Disorders ◽  
Hematological Disorders

Abstract Evolving data demonstrate the pathogenetic significance of chromosomal ends telomeres and telomerase activity in the molecular pathogenesis of many hematological disorders. Furthermore, the presence of eroded telomeres and enhanced telomerase activity in hematopoietic cells has been associated with poor prognosis both in myeloid and lymphoid malignancies. The aim of the present study was to evaluate telomere length and telomerase activity in patients with Ph1-negative Chronic Myeloproliferative Disorders (Ph−-CMPD) either at diagnosis or during the course of the disease and to assess their possible clinical utility. Sixty-six bone marrow and 60 peripheral blood samples were obtained from 80 Ph−-CMPD patients (aged 58.57±16.42 years) and 18 healthy age-matched controls (aged 53.94±15.16 years). Thirty-six patients diagnosed suffering from Polycythemia Vera, 36 from Essential Thombocythemia, 4 from Idiopathic Myelofibrosis and 4 from Unclassified CMPD. Twenty-six samples were studied at diagnosis, whereas 54 during the course of the disease. Telomere length analysis of individual chromosome ends was performed on bone marrow metaphases using Telomere/Centromere Quantitative-Fluorescence In Situ Hybridization (T/C Q-FISH) (Dako A/S, Denmark). Telomerase activity was determined in bone marrow purified CD34(+) and CD20(+) cells as well as in peripheral blood CD3(+) T-lymphocytes and granulocytes with the PCR-based Telomeric Repeat Amplification Protocol (TRAP) assay (Roche, Germany). Gene expression of telomerase-associated proteins (hTERT, hTER, TEP1, TRF-1 and TRF-2) was assayed by Real-Time Multiplex PCR (Maximbio, USA). Ph−-CMPD patients showed significantly more eroded telomeres (P=0.010) and increased telomerase activity in CD34(+) cells (P=0.005) compared to healthy age-matched individuals. However, there was no statistical difference in telomere length (P=0.451) and enzyme activity (P=0.538) among different groups of Ph−-CMPD. Telomerase activity was not detected in the remaining hematopoietic cells both in patients and healthy controls, which was closely correlated with downregulation in hTERT mRNA expression. hTER, TEP1, TRF-1 and TRF-2 showed no apparent differential expression of mRNA in all hematopoietic cell fractions. Chromosomal aberrations (+8, +9, del13q14, del20q12) were found by FISH in 37% Ph−-CMPD patients with reduced telomere lengths (P=0.001) and enhanced telomerase activity (P=0.014), especially during the course of the disease (P=0.028). The patients with shortened telomeres displayed a higher incidence of having thrombotic or hemorrhagic events during follow-up (P=0.011), treatment failure (P=0.024) and disease progression to myelofibrosis, myelodysplastic syndromes, secondary leukemia or death (P=0.137). Nevertheless, telomerase expression was not correlated with the above complications. The event free survival (survival without complications, e.g. myelofibrosis, myelodysplastic syndromes, secondary leukemia and death) was significantly shorter in patients with reduced telomere lengths (Log Rank P=0.033), who demonstrated a 7,71-fold higher probability of having complications within five years from the initial diagnosis (95% CI=2,04–31,49 P<0.001). In conclusion, accelerated telomere shortening may not be prevented or restored by telomerase activity in most of the Ph−-CMPD myeloid cells. Loss of telomere stability seems to predispose to further genetic events such as chromosomal rearrangement and consequently to trigger off a multistage neoplastic transformation of these diseases. Moreover, the negative correlation between telomere length and survival probability of Ph−-CMPD patients is indicative that telomere dynamics may serve as a useful prognostic tool for these patients.

Chronic Myeloproliferative Disorders in Bone Marrow Biopsies

1990 ◽  
Vol 186 (1) ◽  
pp. 3-27 ◽  
Author(s):  
A. Georgii ◽  
K.-F. Vykoupil ◽  
Th. Buhr ◽  
H. Choritz ◽  
U. Döhler ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloproliferative Disorders ◽  
Bone Marrow Biopsies ◽  
Chronic Myeloproliferative Disorders

Prodefensin in Plasma of Patients with Chronic Myeloproliferative Disorders. A Parameter of Myelopoietic Activity.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2233-2233
Author(s):  
Søren Kamp ◽  
Morten Krogh Jensen ◽  
Niels Borregaard
Keyword(s):  
Bone Marrow ◽  
Plasma Concentrations ◽  
Myeloproliferative Disorders ◽  
Cell Stage ◽  
Chronic Myeloproliferative Disorders ◽  
Bone Marrow Plasma ◽  
Order Of Magnitude ◽  
Terminal Amino ◽  
Mean Concentration ◽  
Weight Structures

Abstract Prodefensins (proHNPs) are the 74 aa antimicrobially inactive precursor peptides of defensins (HNPs). ProHNPs are synthesized in neutrophil precursors from the late promyelocytic stage and until the band cell stage. In promyelocytes, proHNP is proteolytically cleaved to yield 29–30 aa HNPs that are efficiently stored in primary (azurophil) granules. Beyond the promyelocytic stage, proHNPs are no longer proteolytically processed and significant amounts of proHNP escape the cell through constitutive exocytosis. The fate and biological implications of proHNP constitutively secreted from myeloid cells is unclear. We have raised antibodies against a synthetic propiece of proHNP (45 N-terminal amino acids) and developed an accurate, sensitive and specific ELISA for proHNP using these antibodies, with a detection limit of 4.0 ng/ml. We found levels of pro HNP in bone marrow plasma of 9 μg/ml and levels in blood plasma of 1.7 μg/ml. This indicates that the bone marrow is an important organ for generation of this pro-antibiotic molecule giving rise to plasma concentrations in the same order of magnitude as lysozyme and hCAP-18. Studies of plasma from patients with ph- chronic myeloproliferative disorders showed a mean concentration of 3.5 μg/ml indicating that proHNP is a parameter of myelopoietic activity. ProHNP in plasma was apparently not complexed to higher molecular weight structures, yet it was not present in urine. This indicates that proHNP from bone marrow is processed in circulation.

scholarly journals Chronic myeloproliferative disorders: the bone marrow stromal component is not involved in the malignant clone

Leukemia ◽  
2007 ◽  
Vol 21 (2) ◽  
pp. 377-378 ◽  
Author(s):  
M Di Ianni ◽  
L Moretti ◽  
B Del Papa ◽  
M De Ioanni ◽  
E Bonifacio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloproliferative Disorders ◽  
Chronic Myeloproliferative Disorders ◽  
Stromal Component
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