Markers of myeloproliferative diseases in childhood polycythemia vera and essential thrombocythemia.
OBJECTIVE
Polycythemia vera (PV) and essential thrombocythemia (ET) can present in pediatric age as sporadic or familial diseases. To define the biologic profile of childhood PV and ET, we evaluated specific markers in a cohort of pediatric patients affected by PV and ET, including cases with familial occurrence.


METHODS
Thirty-eight children with PV and ET were investigated. The control group included 58 adults with PV and ET. Endogenous erythroid colonies, qualitative reverse transcriptase polymerase chain reaction for polycythemia rubra vera-1 (PRV-1) RNA expression, human androgen receptor assay and allele specific polymerase chain reaction for JAK2 V617F mutation were undertaken in all patients. Thrombopoietin, thrombopoietin receptor (c-mpl), and erythropoietin receptor mutation analysis was performed by direct sequencing in familial cases.


RESULTS
The JAK2 V617F mutation in children with PV was significantly less frequent than in adult PV. The most common myeloproliferative marker found in these patients was PRV-1 RNA overexpression. Children and adults with sporadic ET showed a similar proportion of patients with PRV-1 RNA overexpression, JAK2 V617F mutation, and clonality, while none of the familial ET showed JAK2 V617F mutation and clonality. Also, PRV-1 RNA overexpression was significantly less common. Furthermore, most patients with familial ET exhibited the dominant-positive activating mutation of c-mpl. Finally, children with PV and ET had a significant lower incidence of thrombosis than adults.


CONCLUSIONS
This study demonstrates that familial and sporadic ET recognize different pathogenetic mechanisms. Myeloproliferative markers are specific tests for the diagnosis of ET in children with sporadic forms, while a significant proportion of children with PV can prove negative.
Teofili
Luciana
L
Department of Hematology, Catholic University, Rome, Italy.
Giona
Fiorina
F
Martini
Maurizio
M
Cenci
Tonia
T
Guidi
Francesco
F
Torti
Lorenza
L
Palumbo
Giovanna
G
Amendola
Angela
A
Foà
Robin
R
Larocca
Luigi M
LM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D002648:Child; D015331:Cohort Studies; D015672:Erythroid Precursor Cells / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D058851:GPI-Linked Proteins; D006801:Humans; D015994:Incidence; D007519:Isoantigens / Q000097:blood / Q000235:genetics; D053614:Janus Kinase 2 / Q000097:blood / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000097:blood / Q000235:genetics; D010375:Pedigree; D011087:Polycythemia Vera / Q000097:blood* / Q000150:complications / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000097:blood; D011944:Receptors, Androgen / Q000097:blood / Q000235:genetics; D011956:Receptors, Cell Surface / Q000097:blood / Q000235:genetics; D017467:Receptors, Erythropoietin / Q000097:blood / Q000235:genetics; D053628:Receptors, Thrombopoietin / Q000097:blood / Q000235:genetics; D012384:Rome / Q000453:epidemiology; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000150:complications / Q000235:genetics* / Q000473:pathology; D013926:Thrombopoietin / Q000097:blood / Q000235:genetics; D013927:Thrombosis / Q000453:epidemiology / Q000209:etiology; D013997:Time Factors
C410798:AR protein, human; D015415:Biomarkers; C407242:CD177 protein, human; D058851:GPI-Linked Proteins; D007519:Isoantigens; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011956:Receptors, Cell Surface; D017467:Receptors, Erythropoietin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin; C507924:JAK2 protein, human; D053614:Janus Kinase 2