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At least 19 recordsLinked to original sources
PubMed1993

Thromboembolic complications of polycythemia: polycythemia vera versus smokers' polycythemia.

PURPOSE: This report compares patients with the hypercoagulable state of polycythemia vera to patients with secondary polycythemia caused by tobacco use to determine whether the incidence of thromboembolic events is equivalent. METHODS: The medical records of 146 patients with the diagnosis of polycythemia between 1977 to 1990 were reviewed. Patients with transient, relative, or stress polycythemia were excluded from this study as were patients with polycythemia as a result of cardiac or pulmonary anomalies or both. The diagnosis of polycythemia vera (n = 43) was verified by use of the guidelines of the Polycythemia Vera Study Group. The diagnosis of polycythemia caused by smoking (n = 27) was based on an elevated total red blood cell volume, decreased oxygen saturation on arterial blood gas measurement, evidence of chronic obstructive pulmonary disease, and elevated carboxyhemoglobin levels. RESULTS: Twenty-six patients (60%) with polycythemia vera and 11 patients (41%) with smoker's polycythemia had at least one thromboembolic problem. No significant differences existed between the groups with regard to age, hematocrit, or number of cardiac and cerebrovascular events. Overall, patients with polycythemia vera had a greater number of thromboembolic events per patient (p < 0.05) and more peripheral arterial thromboemboli (p < 0.005) than did patients with polycythemia as a result of smoking (Fisher's Exact Test). CONCLUSIONS: Thus the results of this study demonstrate that smokers' polycythemia does not represent a hypercoagulable state equivalent to that of polycythemia vera.

Analysis of Variance↗
PubMed1997

Polycythemia vera. V. Enhanced proliferation and phosphorylation due to vanadate are diminished in polycythemia vera erythroid progenitor cells: a possible defect of phosphatase activity in polycythemia vera.

Erythropoietin (EP) and stem cell factor (SCF) are essential growth factors for erythroid progenitor cell proliferation and differentiation in serum-free culture. It has been previously shown that burst-forming units-erythroid and colony-forming units-erythroid from patients with polycythemia vera (PV) have enhanced sensitivity to EP and SCF compared with normal erythroid progenitors, but little is known about the mechanism for this difference. In the present investigation, the effect of EP and SCF on protein tyrosine phosphorylation in day-8 normal and PV erythroid colony-forming cells, which give rise to colonies of 2-49 hemoglobinized cells, was studied. EP rapidly induced tyrosine phosphorylation of the EP receptor, whereas the most prominent phosphorylated protein induced by SCF was identified as the SCF receptor. No additional phosphorylated proteins were evident when PV cells were compared with normal cells. Culture of normal erythroid progenitors with orthovanadate, an inhibitor of protein tyrosine phosphatases, resulted in an increased number of erythroid colonies and enhanced protein tyrosine phosphorylation. However, in contrast, little enhancement was evident with PV cells. These results indicate that, although vanadate may be acting in normal erythroid progenitors as a phosphatase inhibitor that potentiates the kinase activity induced by SCF and EP, this function is diminished in PV cells. Because erythropoiesis is regulated by a balance between protein tyrosine kinase activity and protein tyrosine phosphatase activity, PV patients may have an abnormal phosphatase activity allowing increased cell proliferation.

Cell Division↗
PubMed2001

The value of bone marrow histology in differentiating between early stage Polycythemia vera and secondary (reactive) Polycythemias.

BACKGROUND AND OBJECTIVES: The diagnostic criteria of the Polycythemia Vera Study Group (PVSG), although generally acknowledged as the gold standard for establishing a diagnosis of polycythemia vera (PV), do not consider bone marrow features. It may, therefore, be speculated that initial-early stages of PV are overlooked. In this retrospective study we tried to investigate whether bone marrow morphology of patients with an only borderline to slight increase in hemoglobin/hematocrit not conforming with the postulates of the PVSG enabled a clear-cut differentiation between PV and secondary (reactive) polycythemias (SP). DESIGN AND METHODS: From a series of 348 patients with a borderline to pronounced erythrocytosis and representative pre-treatment bone marrow trephine biopsies a cohort of 86 cases was selected showing only a borderline increase in hemoglobin (males < 18.5 g/dL, females < 16.5 g/dL). Biopsies and clinical records were evaluated independently and following histologic and clinical work-up a straightforward consensus was reached. The diagnostic impact of histologic findings was tested by means of discriminate analysis of 20 standardized morphologic features based on histochemical and immunohistochemical staining techniques. RESULTS: Bone marrow histopathology in 47 patients diagnosed as having SP was characterized by a minimal to slight increase in cellularity with predominance of the erythroid lineage. Neutrophil granulocytopoiesis was prominent and left-shifted and small to medium-sized megakaryocytes without maturation defects were scattered throughout the bone marrow. There was an increased number of eosinophils, marked perivascular plasmacytosis, histiocytic reticular cells with accumulated cell debris and many iron-laden macrophages. Contrasting this appearance in SP our 39 patients with initial-early stage PV revealed a hypercellular bone marrow with trilineage proliferation (pan-myelosis) showing confluent sheets of erythropoiesis and loose clusters of megakaryocytes. Megakaryocytopoiesis was characterized by a pleomorphous appearance, i.e. giant cells were lying adjacent to small ones, but lacked an obvious cytologic abnormality. There was usually no prominent inflammatory reaction of the interstitial compartment. In ten patients lymphoid nodules were found, but no conspicuous iron deposits and in six patients a borderline to minimal increase in reticulin fibers was present. Following stepwise discriminate analysis of histologic features a set of parameters emerged including increase in megakaryocyte size, perivascular plasma cells, overall bone marrow cellularity and cellular debris. This pattern exerted a significant impact on separation (Wilks' lambda statistics = 0.110, p < 0.0001) of early stage PV from SP. Most patients with SP had an underlying bronchopulmonary condition, frequently associated with heavy smoking or rarely renal pathology. In addition to the histopathologic features, splenomegaly, thrombocyte count, LDH, LAP and erythropoietin levels proved to be different in the two groups of patients. INTERPRETATION AND CONCLUSIONS: Initial-early PV is characterized by a specific pattern of bone marrow histopathology. Clinical features of distinctive impact include splenomegaly, thrombocyte count, LDH, LAP and in particular erythropoietin level. Taking these clinical and histologic findings into consideration, reactive-secondary causes of polycythemia (SP) are clearly distinguishable from autonomous ones (PV).

Adult↗
PubMed1986

Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols.

The PVSG was organized in 1967 to establish effective diagnostic criteria for polycythemia vera, to study the natural history of the disease and to define the optimal treatment. Although polycythemia vera and the other myeloproliferative diseases are relatively uncommon, the PVSG was able to accumulate well over 1,000 patients with these various disorders and to study them according to a total of 15 different protocols. PVSG-01, a long-term randomized controlled study of phlebotomy alone compared with the myelosuppressive agents, 32P or chlorambucil supplemented by phlebotomy, continues to receive follow-up data on 93% of surviving patients 18 years after initiation of the study. During its lifetime, PVSG has developed a widely accepted and highly effective set of criteria for the specific diagnosis of polycythemia vera as well as useful criteria for the diagnosis of essential thrombocythemia. It has gathered an enormous volume of data on the natural history of the myeloproliferative diseases and in particular on the nature of the prevalent complications, such as thrombotic events and hematologic and nonhematologic malignancies. With respect to the final question, the optimal treatment for polycythemia vera, it is apparent that the expectation of a single optimal therapy that would apply to all patients at all ages and stages of the disease was naive. Nevertheless considerable progress has been made. Moreover, the group has defined more precisely than ever before the nature of the complications of the disease and the association of the risks of specific complications with specific forms of therapy. It thus has made it possible to pose the next series of therapeutic questions that must be addressed in this disorder with a greater degree of sophistication than was previously possible.

Acute Disease↗
PubMedDate not supplied

Atrial natriuretic peptide in relative polycythemia and polycythemia vera.

Atrial natriuretic peptide (ANP) levels have been tested in patients with chronic relative polycythemia (RP), polycythemia vera, and in healthy subjects in order to find a possible underlying pathophysiological mechanism for relative polycythemia. No difference in statistical significance has been found between the mean atrial natriuretic peptide levels of the polycythemic patients and the control group. It is suggested that ANP probably plays no significant role in the contraction of plasma volume observed in normotensive patients with RP.

Aged↗
PubMed1988

[Radionuclide study of liver function in polycythemia vera and other types of polycythemia].

Clinico-laboratory and radionuclide (radio-hepatography with 131I-rose bengal and liver scanning with 198Au colloid solution) investigation of liver function was performed in 110 patients with polycythemia vera during exacerbation, in 16 patients with symptomatic erythrocytosis (10--chronic pulmonary disease, 3--polycystic kidney, 2--obesity, 1--peptic ulcer), and in 11 patients with a polycythemic form of myelofibrosis. The results of the radionuclide method showed disturbed liver function in 51 (46.3%) patients with polycythemia, in 4 patients with myelofibrosis and in 3 with erythrocytosis which were characterized by a decrease in hepatocytic absorptive-excretory function and a decrease in the activity of the reticulo-histiocytic stroma. Liver changes depended on a stage of disease and were detected earlier than with the use of biochemical methods. As distinct from erythrocytes, one-type disorders were noted in the patients with myelofibrosis. Correlation in the lever of RP accumulation in the spleen, its sizes and stage of disease was established. Liver function returned to normal after cytostatic therapy in the patients with stage IIA polycythemia, partially IIB stage, during remission.

Adult↗
PubMed1998

Absence of polycythemia in a child with a unique erythropoietin receptor mutation in a family with autosomal dominant primary polycythemia.

Primary familial and congenital polycythemia (PFCP or familial erythrocytosis) is a rare proliferative disorder of erythroid progenitor cells, characterized by elevated erythrocyte mass and hemoglobin concentration, hypersensitivity of erythroid progenitors to erythropoietin (EPO), and autosomal dominant inheritance or sporadic occurrence. A number of EPO receptor (EPOR) mutations were found in subjects with PFCP; most of these mutations resulted in the truncation of the COOH-terminal of the EPOR protein. We studied a family with autosomal dominant inheritance of PFCP in which four subjects were affected in three generations. We screened the affected individuals for EPOR gene mutations using SSCP analysis and found a C5964G mutation in exon VIII that changes tyrosine codon 426 to a translation termination codon resulting in an EPOR protein truncated by 83 amino acids. The mutant C5964G-EPOR exhibited hypersensitive EPO-dependent proliferation compared to the wild-type EPOR when tested in a murine interleukin-3-dependent myeloid cell line (FDC-P1). We also examined the segregation of the mutation with PFCP in the family and found that a child in the third generation inherited the mutation without having laboratory evidence of polycythemia. Further in vitro analysis of the erythroid progenitor cells of this affected child revealed that the progenitor cells were hypersensitive to EPO (a hallmark of PFCP) suggesting the presence of the disease at the level of progenitor cells. Failure of this child to develop polycythemia suggests the existence of as yet unidentified environmental or genetic factors that may suppress disease development.

Adult↗
PubMed2001

Polycythemia rubra vera versus secondary polycythemias. A clinicopathological evaluation of distinctive features in 199 patients.

To determine parameters of distinctive value in polycythemia rubra vera (PV) versus secondary polycythemias (SP), a clinicopathological study was performed on 199 patients. These presented with a borderline to marked elevation of the hemoglobin level (> 18 g/dl in men and > 16 g/dl in women). Evaluations of clinical features and bone marrow histopathology were carried out independently. According to the results derived from laboratory data and representative pretreatment trephine biopsies, three groups of patients emerged: group I presenting with the concordant clinical and morphological findings of early to manifest PV (136 patients), group II consisting of 55 patients with the congruent signs and symptoms of SP mostly caused by various chronic bronchopulmonal disorders, and finally eight patients (group III) with divergent findings. Between group I and II patients (PV versus SP), a number of clinical parameters proved to be significantly different. With the exception, of the red cell mass, platelet count, leukocyte alkaline phosphatase, LDH, spleen size, and the erythropoietin level had a significantly discriminating impact. Morphological features of distinctive value consisted of a set of specific lesions. Contrasting SP with an only borderline to slight increase in cellularity associated with a moderate enlargement of the erythroblastic islets, PV was always characterized by a significant increase in hematopoiesis, revealing a trilinear proliferation (panmyelosis). Megakaryopoiesis was strikingly different in PV as compared to SP by displaying clustering and a pleomorphous appearance. i.e., very small and giant megakaryocytes with staghorn-like nuclei were neighboring each other. Moreover, conspicuous alterations of the interstitial compartment were recognizable in SP. These consisted of deposits of cell debris in histiocytic reticular cells, iron-laden macrophages, and a plasmacytosis, implying an inflammatory reaction. These changes were only very rarely observed in PV, as opposed to a minimal to slight increase in reticulin fibers in about 12% of patients. In conclusion, a more elaborate evaluation of bone marrow features resulted in a set of diagnostic criteria with discriminating capacity that should be considered in prospective clinical trials.

Bone Marrow↗
PubMed2002

The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members' practice patterns.

The Polycythemia Vera Study Group (PVSG) was organized in 1967 to identify the optimal approach to the diagnosis and treatment of polycythemia vera (PV). Nevertheless, a systematic assessment of US physicians' approach to PV has not been performed. To determine practice patterns in the management of PV, a random sample of the US American Society of Hematology (ASH) membership was surveyed. Thirty-three percent of 3000 surveys were returned. Significant variations in diagnostic and therapeutic approach were evident by region, practice type, specialty, and clinical experience. Red cell volume determinations (78% of respondents), serum erythropoietin levels (76%), and arterial blood gases (75%) were the most frequent tests used in the diagnosis of PV. Sixty-nine percent of physicians use phlebotomy as their first choice for erythrocytosis. Phlebotomy plus hydroxyurea (27.8%) and hydroxyurea alone (10%) were used less often. Despite PVSG recommendations, almost 16% of physicians used a target hematocrit of 0.55 (50%) or 0.55 (55%) for phlebotomy therapy. Eighty-two percent of physicians treated thrombocytosis only when platelet counts exceeded 1000 x 10(9)/L (1 000 000/microL) or in the event of symptoms. Hydroxyurea (62.8%) and anagrelide (35.4%) were the primary agents used to treat thrombocytosis. Thus, this national survey of US hematologists and oncologists has identified substantial variation in the approach to the diagnosis and treatment of PV. A significant minority of physicians undertreat erythrocytosis, and little consensus exists regarding the treatment of thrombocytosis.

Data Collection↗
PubMed1987

Differential polycythemia: a comparative study between spurious polycythemia and pure erythrocytosis.

The definite differential diagnosis between spurious polycythemia (SP) and pure erythrocytosis (PE) was tested. Serum erythropoietin (EPO) levels in 6 patients with PE were 12.8 +/- 3.7 mU/ml and were significantly lower than those of both 19 normal controls (28.5 +/- 15.0 mU/ml) and 9 patients with SP (21.3 +/- 10.2 mU/ml). Three of 11 patients with SP and 1 of 3 patients with PE had significantly higher marrow erythroid progenitor cells (CFU-Es) than those of the normal controls. Spontaneous CFU-E growth (CFU-E growth in the absence of added EPO) was found in 4 of 11 patients with SP, 1 of 3 patients with PE, and all patients with polycythemia vera. However, the number of spontaneous CFU-E was low in SP and PE. The measurements of serum EPO levels and CFU-E growth did not provide differentiation between PE and SP. Even if some patients, whose total red cell volumes are either higher than 12.5% above the mean predicted values or their CFU-E growth is great, are diagnosed as SP, consideration should be made that they might, in fact, have PE.

Adult↗
PubMed1991

[Effect of bloodletting on the proliferative activity of erythroid progenitor cells from the bone marrow of patients with polycythemia and polycythemia vera].

We assessed the effect of phlebotomy on the proliferative activity of less (BFU-E) and more (CFU-E) mature bone marrow-derived erythroid progenitors from patients with polycythemia vera (PV) and polycythemia symptomatic (PS) in vivo in diffusion chamber culture. The cloning efficiency of erythroid progenitors under the effect of normal and increased erythropoietin (Epo) concentrations in PS was comparable with controls, whereas in PV the BFU-E and CFU-E-derived colony formation was significantly higher (p less than 0.01). In PV, the erythroid progenitors formed markedly more colonies in cultures stimulated with higher Epo concentration (p less than 0.01). The results of this study indicate that phlebotomy both in PV and PS does not affect the reactivity of erythroid progenitors to various Epo concentrations.

Adult↗
PubMed1993

RES scintigraphy in polycythemia vera and secondary or relative polycythemia.

Scintigraphy of the reticuloendothelial system (RES) was performed in 19 patients with polycythemia vera (PCV) and in 18 with secondary or relative polycythemia (PS). Bone marrow extension was found in all patients with PCV and in 11 of 18 patients with PS. The patients with PCV had a higher degree of extension than those with PS. Increased pelvic bone marrow activity was found in 16 of 19 PCV patients, but in none with PS. Splenomegaly was found in 9 patients with PCV, and in none with PS. It is concluded that RES scintigraphy in the majority of patients may differentiate between PCV and PS using the parameters pelvic bone marrow activity, bone marrow extension and splenic size.

Adult↗
PubMed1984

Increased prevalence of polycythemia vera in parents of patients on polycythemia vera study group protocols.

An investigation of relatives of 652 patients entered on studies of the Polycythemia Vera Study Group yielded five documented cases of the disease among the parents of patients. When compared with expected values based on the Connecticut Tumor Registry and other population studies a significant increase was found in the lifetime incidence of polycythemia vera in parents of these patients.

Adult↗
PubMed1989

Comparison of erythroid progenitor cell growth in vitro in polycythemia vera and chronic myelogenous leukemia: only polycythemia vera has endogenous colonies.

The ability of erythroid cultures to distinguish among myeloproliferative disorders was examined. We studied 14 patients with polycythemia vera (PV), 11 with chronic myelogenous leukemia (CML), four with non-PV erythrocytosis, two with agnogenic myeloid metaplasia, as well as three normal fetuses and greater than 25 normal adults. Endogenous, i.e. grew without added erythropoietin, bone marrow CFU-E-derived colonies were observed in all but one PV patient. However, endogenous blood BFU-E-derived bursts were observed in only eight of 14 PV patients. Endogenous erythroid colonies were not seen in cultures from any normal adults or fetuses, or patients with CML, erythrocytosis, or myeloid metaplasia. In PV, relative HbF synthesis was always greater in cultures without erythropoietin, while in cultures from all other patients relative HbF synthesis was similar to that observed in cultures from normal individuals. We conclude that PV and CML are distinguishable in culture since CML patients do not have endogenous growth. Most important, endogenous bone marrow CFU-E-derived colonies are the only consistently unique observation in patients with PV, and endogenous CFU-E- and BFU-E-derived colonies and bursts are not uniformly observed in PV blood cultures. In-vitro studies of erythropoiesis to confirm the diagnosis of PV, therefore, require marrow when endogenous colonies and bursts are absent from blood cultures.

Adolescent↗
PubMed1999

Polycythemia vera megakaryocytes store and release lysozyme to a higher extent than megakaryocytes in secondary polycythemia (polyglobuly).

Lysozyme, a myelomonocytic marker not only exerts bacteriolytic, but also immunomodulatoric properties and was found to bind to the glycosaminoglycan serglycin, an important constituent of the extracellular matrix (ECM). Pathological serum lysozyme levels were described in chronic myeloproliferative disorders (CMPDs) and other hematological conditions. In this context it is remarkable that in polycythemia rubra vera (PV), characterized by a proliferation particularly of the megakaryo- and erythropoiesis, serum lysozyme levels behave independently of the numbers of myelomonocytic cells in peripheral blood. To elucidate whether megakaryopoiesis might be the source of the increased serum lysozyme, we performed an experimental study on isolated and enriched megakaryocytes derived from bone marrow of patients with PV. Findings were compared to a group of patients with reactive (smoker's) polyglobuly (PG). In confirmation of previous results, quantification of serum lysozyme levels showed a slight elevation in the cohort of PV patients which was not correlated with the leukocyte count. Applying an immunohistochemical assay we were able to demonstrate intracytoplasmic lysozyme storage in megakaryocytes. Moreover, performing the reverse hemolytic plaque assay (RHPA), a technique which enables detection of secreted proteins at the single cell level, we found that 54% of the PV, but only 3% of the PG megakaryocytes spontaneously secreted lysozyme. After rhIL-3 treatment the secretion of lysozyme remained unchanged in PV but increased to 14% in PG. These findings suggest that the extent of megakaryocytic lysozyme secretion might discriminate PV from reactive conditions. Although a direct involvement of lysozyme in the regulation of aberrant megakaryopoiesis in PV is not likely, the results of the present study point to the possibility that lysozyme could be involved in the interactions of PV megakaryocytes with ECM. Moreover, the response to rhIL-3 significantly discriminates PV megakaryocytes from megakaryocytes of the PG group.

Female↗
PubMed1994

[A clinical study of sixteen polycythemia vera cases--acute myeloblastic leukemia in patients with polycythemia vera].

The clinical course of 16 patients with polycythemia vera (PV), treated in the period 1982 to 1993, was shown. Splenomegaly occurred in three fourths of these patients (75%), and hypertension was a major symptom. Thrombosis such as myocardial infarction and cerebral infarction was noted. Eight patients was treated with myelosuppressive agents and the 8 other patients were treated with phlebotomy. A 70-year-old male who was treated with mitobronitol (DBM) developed acute myeloblastic leukemia (AML) 11 years later. He was treated with multi-combination chemotherapy (BHAC-DMP), and entered complete remission, followed by early relapse. He became refractory to chemotherapy and died of acute pneumonia 6 months later. Median survival of 16 cases of PV was more than 10 years, and long-term treatment and care are necessary.

Adult↗
PubMed1997

Treatment of polycythemia vera: use of 32P alone or in combination with maintenance therapy using hydroxyurea in 461 patients greater than 65 years of age. The French Polycythemia Study Group.

Despite myelosuppression, polycythemic (PV) patients greater than 65 years of age have a high risk of vascular complications, and the leukemic risk exceeds 15% after 12 years. Is the addition of low-dose maintenance treatment with hydroxyurea (HU) after radiophosphorus (32P) myelosuppression able to decrease these complications? Since the end of 1979, 461 patients were randomized to receive (or not) low-dose HU (5 to 10 mg/kg/d), after the first 32P-induced remission, and were observed until death or June 1996. Maintenance treatment very significantly prolonged the duration of 32P-induced remissions and reduced the annual mean dose received to one-third. However, despite this maintenance, 25% of the patients had an excessive platelet count and the rate of serious vascular complications was not decreased, except in the most severe cases with short-term relapse of polycythemia. Furthermore, the leukemia rate was significantly increased beyond 8 years and a significant excess of carcinomas was also observed. The continuous use of HU did not decrease the risk of progression to myelofibrosis (incidence of 20% after 15 years). Life expectancy was shorter (a median of 9.3 years v 10.9 years with 32P alone), except in the most severe cases (initial 32P-induced remission lasting <2 years) in which maintenance treatment moderately prolonged the survival by reducing the vascular risk. In most cases of PV, in which the duration of the first 32P-induced remission exceeded 2 years, the introduction of HU maintenance did not reduce the vascular risk. Although it considerably decreased the mean dose of 32P received, HU maintenance therapy significantly increased the leukemia and cancer risks and reduced the mean life expectancy by 15%. However, in cases with more rapid recurrence, the introduction of maintenance treatment reduced the vascular risks and moderately prolonged survival. The use of HU as a maintenance therapy is therefore only justified in this situation.

Actuarial Analysis↗
PubMed1997

The erythropoietin receptor gene is not linked with the polycythemia phenotype in a family with autosomal dominant primary polycythemia.

Primary familial and congenital polycythemia (PFCP or familial erythrocytosis) is a rare hematological disorder with either autosomal-dominant inheritance or sporadic occurrence. It is characterized by an increased proliferation of erythroid precursors that results in an elevated red blood cell mass. In some of the PFCP families, the disease phenotype is associated with mutations of the erythropoietin receptor (EPOR). Mutations in other genes are likely to cause PFCP as well, but no evidence so far has been provided to support this contention. In this study, we present a family in which 6 of 15 family members were affected in three generations. We screened exon VIII of the EPOR gene for mutations and found a C-->T substitution (C6148T) in the maternal grandmother of the propositus. The mutated allele of the affected grandmother was not passed to either of her two affected children or to her one healthy child; thus, the disease phenotype was not linked to the C6148T mutation in this family. Further examination of the inheritance of the EPOR gene alleles and sequence analysis ruled out linkage between the disease phenotype and the EPOR gene; therefore, an abnormality in another gene must be the cause of PFCP in this particular family. In three affected family members tested, erythroid progenitors were hypersensitive to EPO. This in vitro behavior of the progenitors confirms the diagnosis of PFCP in these subjects. Moreover, it suggests a dominant lesion of an as-yet unidentified gene, either at the level of the EPOR-signaling pathway or another erythropoiesis-regulating pathway that may be responsible for enhanced proliferation of the erythroid progenitors.

Cells, Cultured↗