2. HEMATOPOIESIS.ppt

7/25/2019 2. HEMATOPOIESIS.ppt

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BLOOD CELL

FORMATION(HEMATOPOIESIS)



I. INTRODUCTION

A. Definition

Hematopoiesis is the proliferation ofHematopoiesis is the proliferation ofprogenitor cells, which are maintained bprogenitor cells, which are maintained b

the stem cells and their differentiation intothe stem cells and their differentiation into

all the cell!lar components of blood.all the cell!lar components of blood.

". #ites of hematopoiesis". #ites of hematopoiesis →→ depend on thedepend on the

presence of disease and on the de$elop%presence of disease and on the de$elop%

mental state of the indi$id!al.mental state of the indi$id!al.

&. Normal conditions&. Normal conditions →→ originate in the boneoriginate in the bone

marrow marrow



#ome components 'e.g., erthroctes and#ome components 'e.g., erthroctes and

platelets( complete their de$elopment atplatelets( complete their de$elopment at

med!llarmed!llar 'i.e., bone marrow( sites, whereas'i.e., bone marrow( sites, whereas

other components 'e.g., T and " cells(other components 'e.g., T and " cells(

complete their de$elopment atcomplete their de$elopment at e)tramed!llar.e)tramed!llar.

*oet!s*oet!s + - months+ - months →→ ol/ sacol/ sac

- 0 months - 0 months →→ li$er, spleenli$er, spleen

1 - 2 months1 - 2 months →→ bone marrowbone marrow

InfantsInfants ++ "one marrow 'practicall all bones( "one marrow 'practicall all bones(

Ad!lts Ad!lts + $ertebrae, ribs, stern!m, s/!ll,+ $ertebrae, ribs, stern!m, s/!ll,

sacr!m, pro)imal ends of fem!r sacr!m, pro)imal ends of fem!r



. Disease. Disease

In the presence of disease, e)tramed!llarIn the presence of disease, e)tramed!llar

sites can ser$e as primar sites of bloodsites can ser$e as primar sites of blood cellcell

de$elopment.de$elopment.

II. "ON3 4ARRO5II. "ON3 4ARRO5

A. #tem cells A. #tem cells ≈≈ C*U 'Colon % *orming Unit(C*U 'Colon % *orming Unit(

areare fo!nd within the "4 as the origin of allfo!nd within the "4 as the origin of all bloodblood

cells.cells.



6 "lood cells are formed b a process of6 "lood cells are formed b a process of

differentiation from the least de$eloped stemdifferentiation from the least de$eloped stem

cells to highl speciali7ed blood cells.cells to highl speciali7ed blood cells. 'Table &('Table &(

6 #tem cells6 #tem cells ++

&.&. pl!ripotential stem cellspl!ripotential stem cells →→ 88 main marrowmain marrowcell lines +cell lines +

a(. erthroctes 'red cells(a(. erthroctes 'red cells(

b(. gran!loctes - monoctes 'white cells(b(. gran!loctes - monoctes 'white cells(

c(. thromboctes 'platelets( and probablc(. thromboctes 'platelets( and probabl

lmphoctes 'T 9 " lmp.,plasma cells(. lmphoctes 'T 9 " lmp.,plasma cells(.



. 4!ltipotential stem cells. 4!ltipotential stem cells →→ meloidmeloid m!lti%m!lti%

potential stem cellspotential stem cells andand lmphoidlmphoid m!ltipoten%m!ltipoten%

tial stem cells.tial stem cells.

% 4eloid m!ltipotential stem cells% 4eloid m!ltipotential stem cells ++

: C*U%;344 'C*U%#(: C*U%;344 'C*U%#( →→ C*U gran!loctes,C*U gran!loctes,

erthroctes, monoctes anderthroctes, monoctes and

mega/aroc%mega/aroc% tes< the earliesttes< the earliestdetectable meloid prec!rsordetectable meloid prec!rsor

: C*U%C 'C*U%;4(: C*U%C 'C*U%;4( →→ C*U % gran!loctesC*U % gran!loctes

and monoc tesand monoc tes



: C*U%3 and "*U%3: C*U%3 and "*U%3

% C*U%3% C*U%3 →→ C*U - erthropoiesisC*U - erthropoiesis

% "*U%3% "*U%3 →→ "!rst"!rst %% *orming Unit % erthroid*orming Unit % erthroid →→

committed to erthropoiesis andcommitted to erthropoiesis and

prec!rsor ofprec!rsor of the C*U%3 the C*U%3

% C*U%3 and "*U%3 are dependent on 3po% C*U%3 and "*U%3 are dependent on 3po

: C*U%4eg: C*U%4eg

% progenitor of mega/aroctes% progenitor of mega/aroctes

% deri$es from C*U%;344% deri$es from C*U%;344 % controlled b thrombopoietin% controlled b thrombopoietin

Figure 1. Schematically summarizes the role of the majorFigure 1. Schematically summarizes the role of the major

progenitor cells of hematopoiesis progenitor cells of hematopoiesis



PluripotentPluripotent

stem cellstem cell

CFUCFUGEMMGEMM LymphoiLymphoi

stem cellstem cell

!FU!FUEE CFU CFUGMEoGMEo CFU CFU"aso"aso

ErythroiErythroi CFU CFUEoEo

ProgenitorsProgenitors CFU CFUMegMeg CFU CFUGMGM

CFUCFUEE

#hymus#hymus

CFU$MCFU$M CFU$G CFU$G

%e Cells%e Cells Platelets Mono$ &eutro$ Platelets Mono$ &eutro$ Eosino$Eosino$ !aso$ !aso$ Lymphocytes Lymphocytes F'GU%E 1.F'GU%E 1. cytes philscytes phils philsphils phils phils

" T



Tabel &. #ome hematopoietic progenitors cells

Term Term Required stimulusRequired stimulus Postulated RolePostulated Role

CFU$LMCFU$LM Multiple GFMultiple GF Pluripotent stem cellPluripotent stem cell

CFU$CFU$GEMMGEMM

(CFU$S)(CFU$S)

GM$CSF* G$CSF*GM$CSF* G$CSF*

M$CSF* 'L$+M$CSF* 'L$+

Pluripotent stem cellPluripotent stem cell

CFU$GMCFU$GM(CFU$C)(CFU$C)

GM$CSF* G$CSF*GM$CSF* G$CSF*M$CSF* 'L$+M$CSF* 'L$+

Committe progenitor ofCommitte progenitor ofgranulopoiesisgranulopoiesis

!FU$E!FU$E Erythropoietin* helper #Erythropoietin* helper #lymphocytes ('L$1* GM$lymphocytes ('L$1* GM$CSF* 'L$+* 'L$,)CSF* 'L$+* 'L$,)

Committe progenitor ofCommitte progenitor oferythropoiesis (early)erythropoiesis (early)

CFU$ECFU$E ErythropoietinErythropoietin Committe progenitor ofCommitte progenitor oferythropoiesis (late)erythropoiesis (late)

CFU$ MegCFU$ Meg 'L$+* GM$CSF* G$CSF.'L$+* GM$CSF* G$CSF.throm"opoietinthrom"opoietin

Committe progenitor ofCommitte progenitor ofthrom"opoiesisthrom"opoiesis



6 =mphoid m!ltipotential stem cells6 =mphoid m!ltipotential stem cells →→ lea$elea$e

the bone marrow and complete diff. inthe bone marrow and complete diff. in

lmph nodes '" cells( and thm!s 'T cells(lmph nodes '" cells( and thm!s 'T cells(

". Hematopoietic ;rowth *actors ≈ C#* 'Colon%

stim!lating factor(

Classification +Classification +

a. Non%lineage%specific ;*a. Non%lineage%specific ;* →→ act on pl!ripo%act on pl!ripo%tential and m!ltipotential stem cells totential and m!ltipotential stem cells to

initiate self%renewal and differentiationinitiate self%renewal and differentiation



6 I=%8 '4!lti%C#*(6 I=%8 '4!lti%C#*( →→ ind!ces the formationind!ces the formation

ofof colonies gran!locte, monoctes,colonies gran!locte, monoctes,

eosinophils, erthroid cells,mega/arocteseosinophils, erthroid cells,mega/aroctesand mast cells prod!ction and mast cells prod!ction

6 ;4%C#*6 ;4%C#* →→ stim!lates gran!lopoiesis andstim!lates gran!lopoiesis and

macrophage prod!ction macrophage prod!ction

b. =ineage%specific ;*b. =ineage%specific ;* →→ act on the commit% act on the commit%

ted progenitor cells and are in$ol$ed in theted progenitor cells and are in$ol$ed in thediff.diff. andand mat!ration of blood cells in themat!ration of blood cells in the

laterlater stages ofstages of hematopoiesis.hematopoiesis.



These factors incl!de +These factors incl!de +

6 3po6 3po →→ stim!lates erthropoiesis, mediatesstim!lates erthropoiesis, mediates

its feed%bac/ controlits feed%bac/ control

6 ;%C#*6 ;%C#* →→ ind!cing formation of gran!locteind!cing formation of gran!locte andand

stim!lates proliferation of some le!/e%stim!lates proliferation of some le!/e% mic cellsmic cells

66 4%C#*4%C#* →→ infl!encing macrophage prod.infl!encing macrophage prod.

6 Thrombopoietin6 Thrombopoietin →→ infl!encing C*U%megainfl!encing C*U%mega 'Table'Table

((



Table . 4eloid Hematopoietic ;rowth *actor

Factor Factor Major !iological -ctiities in /ioMajor !iological -ctiities in /io

ErythropoietinErythropoietin

(Epo)(Epo)

Stimulates erythropoiesis. Meiates its fee"ac0Stimulates erythropoiesis. Meiates its fee"ac0controlcontrol

GM$CSFGM$CSF Stimulates granulopoiesis an macrophageStimulates granulopoiesis an macrophageprouctionprouction

G$CSFG$CSF Stimulates granulopoiesis an proliferation ofStimulates granulopoiesis an proliferation ofsome leu0emic cellssome leu0emic cells

M$CSFM$CSF Stimulates macrophage prouctionStimulates macrophage prouction

'L$+ (Multi$CSF)'L$+ (Multi$CSF) Stimulates granulocyte* monocyte* eosinophils*Stimulates granulocyte* monocyte* eosinophils*erythroi cells* mega0aryocyte an mast cellserythroi cells* mega0aryocyte an mast cells

prouctionprouction

#hrom"opoietin#hrom"opoietin 'nfluencing CFU$mega'nfluencing CFU$mega



C.C. =mpho/ines and mono/ines=mpho/ines and mono/ines

% released b lmphoctes and monoctes% released b lmphoctes and monoctes

'macrophages('macrophages( →→ ha$e wide%rangingha$e wide%ranging

h.poietic effects thro!gh e)tensi$e networ/h.poietic effects thro!gh e)tensi$e networ/

of interaction in$ol$ing imm!ne responsesof interaction in$ol$ing imm!ne responses

to infection and t!mor in$asion.to infection and t!mor in$asion.



%% I= 'Interle!/in(I= 'Interle!/in( + secreted b lmphoctes,+ secreted b lmphoctes,

affect the f!nction of other le!/octes 'com%affect the f!nction of other le!/octes 'com%

m!nication lin/s between le!/octes(m!nication lin/s between le!/octes(

%% engage in comple) interactions with other I=,engage in comple) interactions with other I=,

H;* and man other protein s!ch a TN* andH;* and man other protein s!ch a TN* and

lmphoto)inslmphoto)ins 'Table 8('Table 8(



Table 8. =mphoid Hematopoietic ;rowth *actors

NameName #o!rce#o!rce *!nction*!nction

'L $ 1'L $ 1 Macrophages* #Macrophages* #an ! cells*an ! cells*fi"ro"lastsfi"ro"lasts

Stimulates groth of # an ! cells*Stimulates groth of # an ! cells*meiates inflammation* inhi"its groth ofmeiates inflammation* inhi"its groth ofsome cancer cells.some cancer cells.

'L $ 2'L $ 2 (#(#

cells GF)cells GF)

# cells# cells !ins to receptors on cytoto3ic # cells*!ins to receptors on cytoto3ic # cells*promote their groth* stimulates groth ofpromote their groth* stimulates groth ofhelper # cells.helper # cells.

'L $ ,'L $ , # cells* &4 cells*# cells* &4 cells*mast cellsmast cells

Stimulates 5 regulates groth an iff. of #Stimulates 5 regulates groth an iff. of #an ! cells* eosinophils an "asophils.an ! cells* eosinophils an "asophils.

'L 6 7'L 6 7

(Eo6GF)(Eo6GF)

# cells# cells %egulates prouction of eosinophils.%egulates prouction of eosinophils.-ctiates mature eosinophils.-ctiates mature eosinophils.

'L $ 8'L $ 8 Lymphocytes*Lymphocytes*fi"ro"lastsfi"ro"lasts

Promotes macrophage formation.Promotes macrophage formation.Stimulates 'gG prouction "y ! cells.Stimulates 'gG prouction "y ! cells.

'L$9'L$9 Stromal CellsStromal Cells Supports long$term surial of ! an #Supports long$term surial of ! an #cells in itro.cells in itro.

'L $ :'L $ : Fi"ro"lasts*Fi"ro"lasts*

asc. enot.asc. enot.

Enhancement of neutrophil functionEnhancement of neutrophil function



Common ;eneral *eat!res of

Hematopoietic ;rowth *actors

&.&. All are glcoproteins All are glcoproteins

.. Reg!lators of blood cell de$elopment andReg!lators of blood cell de$elopment and

mat!ration and enhancers of mat!re cellmat!ration and enhancers of mat!re cellf!nctions, which are acti$e at $er lowf!nctions, which are acti$e at $er low

concentrationconcentration

8.8. Acti$e both in $itro and in $i$o Acti$e both in $itro and in $i$o

>.>. ?rod!ced b cells of man tpes?rod!ced b cells of man tpes



1.1. Us!all ha$e both !ni@!e andUs!all ha$e both !ni@!e and

o$erlapping specificitieso$erlapping specificities

.. Acti$e on both stem 'progenitor( cells Acti$e on both stem 'progenitor( cells

and end cellsand end cells

0.0. "iologic affects are mediated after"iologic affects are mediated after

binding to a small n!mber of specificbinding to a small n!mber of specific

high % affinit receptors on the s!rfaceshigh % affinit receptors on the s!rfaces

of target cellsof target cells



B.B. Also bind to receptors on some nonhema Also bind to receptors on some nonhema

% topoietic cells. The significance of this is% topoietic cells. The significance of this is

!n/nown!n/nown

2.2. Displa snerg or additi$e effects withDispla snerg or additi$e effects with

other growth factor other growth factor

&.&. Also act on neoplastic co!nterparts of Also act on neoplastic co!nterparts ofnormal cell tpenormal cell tpe



III. #?=33N

The chief organ of R3#, which alsoThe chief organ of R3#, which alsoincl!des "4, lmph nodes, li$er, circ!latingincl!des "4, lmph nodes, li$er, circ!lating

monoctes and fi)ed tiss!e macrophages.monoctes and fi)ed tiss!e macrophages.

Its chief role in hematopoiesis occ!rs inIts chief role in hematopoiesis occ!rs in

!tero < its postnatal participation is limited.!tero < its postnatal participation is limited.

3)tramed!llar hematopoieis in the spleen3)tramed!llar hematopoieis in the spleenocc!rs in se$eral circ!mstancesocc!rs in se$eral circ!mstances



*!nctions +*!nctions +

?articipates in imm!nologic and phagoctic?articipates in imm!nologic and phagoctic

acti$itiesacti$ities

?rod!ces stem cells?rod!ces stem cells →→ capable ofcapable of

differentiating along hematopoietic, histiocticdifferentiating along hematopoietic, histioctic

and fibroblastic cell linesand fibroblastic cell lines

?la roles in the a!toantibod response and?la roles in the a!toantibod response and

determining blood $ol!me.determining blood $ol!me.



I. 3A=UATION O* TH3 "ON3 4ARRO5

&. Indication for a bone marrow aspirate +&. Indication for a bone marrow aspirate +

3$al!ation of decreased n!mbers of cells3$al!ation of decreased n!mbers of cells

from a single lineagefrom a single lineage3$. of patients with decreased blood cell3$. of patients with decreased blood cell

co!nts 'bictopenia or panctopenia( andco!nts 'bictopenia or panctopenia( and

le!/emias 'stem cell defects 9 disorder(le!/emias 'stem cell defects 9 disorder(

3$. of iron stores and abnormal iron in3$. of iron stores and abnormal iron in

erthroid prec!rsor erthroid prec!rsor



Diagnosis of t!mor in$ol$ementDiagnosis of t!mor in$ol$ement

To demonstrate possible infection bTo demonstrate possible infection b

intracell!lar organismintracell!lar organism

To in$estigate an imm!nologic disorder To in$estigate an imm!nologic disorder

Diagnosis of nonhematopoietic diseasesDiagnosis of nonhematopoietic diseases

. Indications for a "4 biops. Indications for a "4 biops

*ail!re to obtain an ade@!ate marrow*ail!re to obtain an ade@!ate marrow

aspirateaspirate



3$al!ation of panctopenia or bictopenia3$al!ation of panctopenia or bictopenia

=e!/oerthroblastic findings in the=e!/oerthroblastic findings in the

peripheral blood smear peripheral blood smear

3$al!ation of hematologic malignancies3$al!ation of hematologic malignancies

and t!mor stagingand t!mor staging

To defined endpoint of aplasiaTo defined endpoint of aplasia



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2. HEMATOPOIESIS.ppt

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