Rev. Bras. Hematol. Hemoter. vol.36 número5

rev bras hematol hemoter. 2014;36(5):311–312

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

w w w . r b h h . o r g

Scientific

comment

Does

angiogenesis

matter

in

primary

myelofibrosis?

夽

Paulo

Vidal

Campregher

HospitalIsraelitaAlbertEinstein(HIAE),SãoPaulo,SP,Brazil

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Articlehistory:

Received29May2014 Accepted6June2014 Availableonline17July2014

Primarymyelofibrosis(PMF)isaclonalhematopoieticdisorder characterizedbyaninitialprefibroticproliferativephasethat overtimeprogressestobonemarrowfibrosis,extramedullary hematopoiesis,peripheralbloodcytopeniasandanincreased riskofdeveloping acutemyeloidleukemia (AML).Inrecent years,themolecularmechanismsthatcausePMFhavebeen extensivelystudiedandthegenomicchangesthatcausethe diseasehavebeenwidelyelucidated.1

A unique feature of PMF is a systemic inflammatory reactionthat manifests,amongother things, through high serum levels of inflammatory cytokines and chemokines, and a stromal bone marrow reaction involving collagen deposition and increased vascular proliferation.2,3 _There

is now convincing evidence that megakaryocytes play a major role in this stromal reaction.4,5 _{More specifically,}

megakaryocytesfrompatientswithPMFproducehighlevels of inflammatory cytokines including transforming growth factor-beta1(TGF␤1).6_{Recently,PMFsystemicinflammatory}

reaction has taken center stage after a suggestion that a possible mechanism by which ruxolitinib, a JAK1 and JAK2 inhibitor, increases overall survival, is through its

DOIoforiginalarticle:http://dx.doi.org/10.1016/j.bjhh.2014.07.010.

夽

SeepaperbyPanceCCetal.onpages322–8.

Correspondingauthorat:HospitalIsraelitaAlbertEinstein,Av.AlbertEinstein,627/701,BlocoD,1◦_{andar,BiologiaMolecular-LATE/IIEP,}

05652-900SãoPaulo,SP,Brazil.

E-mailaddress:paulo.campregher@einstein.br(P.V.Campregher).

anti-inflammatoryeffect,asthismedicationonlymarginally decreasesthediseaseburden.7

While the diagnosis of advanced PMF is not a major challenge,thedifferentialdiagnosisbetweenprefibroticPMF and essential thrombocythemia (ET), a related neoplastic disease, is not always easy,8 _{since both diseases are}

characterizedbyhighplateletcounts,increasedbonemarrow cellularity,andincreasednumberofatypicalmegakaryocytes in the bone marrow. The importance of making such differentiationisfundamental,sincemostpatientswithET haveabenigndiseasewhilePMFpatientshaveasubstantial decreaseinoverallsurvival.9,10

In this issue of the Revista Brasileira de Hematologiae Hemoterapia(RBHH),Ponceetal.evaluatedtheexpressionof anti-latency-associatedpeptide(LAP)humanTGF␤1inbone marrowmegakaryocytesaswellasthemicrovasculardensity (MVD) inbonemarrowbiopsiesfrom patientswithET and PMF.11 _{Althoughthe number ofpatientswas small,oneof}

themainfindingsofthestudywasthatMVDissignificantly increasedinprefibroticPMFcomparedtoET.Sincethereis no objective wayofhistologicallydifferentiating prefibrotic

http://dx.doi.org/10.1016/j.bjhh.2014.07.009

312

PMFfromET,theadditionofanoveldiagnostictoolthatmay contributetothisdifferentiationiswelcomed.Ifthefinding ofincreasedMVDobservedpredominantly inpatientswith prefibrotic PMF in this study can be reproduced by other authors,itcouldserveasanotherdiagnosticmarker,withthe potentialtoimprovethepathologist’sabilitytodifferentiate betweenthesetwoconditions.Recently,immunostainingfor nuclearfactor,erythroid-derived2(NF-E2)onbonemarrow biopsies has shown to be a promising technique to help differentiatebetweenprefibroticPMFandET.12

Another finding of the study of Ponce et al. was therelationshipbetweenmegakaryocyteTGF␤1expression, MVD and bone marrow fibrosis, suggesting a possible mechanismbywhichincreasedlevelsofTGF␤1producedby megakaryocytescan induce an inflammatoryreaction that culminatesinnewvesselformationandfibrosis.11_Although

nocausalrelationshipcanbedetermined,thisfindingaddsto theliterature,pointingtoaroleforTGF␤1ontheprocessof neo-angiogenesisandfibrosisinhumanandanimalmodels ofPMF.6,13

Inconclusion,thesefindings maycontributetoimprove ourabilitytodifferentiatepatientswithprefibroticPMFandET andalsoreaffirmsapossibleroleofTGF␤1inneo-angiogenesis inPMF.

Conflicts

of

interest

Theauthordeclaresnoconflictsofinterest.

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