Table Of ContentCancer Treatment and Research
SeriesEditor
StevenT.Rosen
RobertH.LurieComprehensive
CancerCenter
NorthwesternUniversity
Chicago,IL
USA
Forfurthervolumes,goto
http://www.springer.com/series/5808
Lalitha Nagarajan
Editor
Acute Myelogenous
Leukemia
Genetics, Biology and Therapy
1 3
Editor
LalithaNagarajan
DepartmentofGenetics
UniversityofTexasMD
AndersonCancerCenter
Unit1006
1515HolcombeBoulevard
HoustonTX77030
USA
[email protected]
ISSN0927-3042
ISBN978-0-387-69257-9 e-ISBN978-0-387-69259-3
DOI10.1007/978-0-387-69259-3
SpringerNewYorkDordrechtHeidelbergLondon
LibraryofCongressControlNumber:2006939515
#SpringerScienceþBusinessMedia,LLC2010
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Contents
TheLeukemiaStemCell...................................... 1
ZeevEstrov
EpigeneticMechanismsinAML–ATargetforTherapy ............. 19
YasuhiroOkiandJean-PierreJ.Issa
ChromosomalTranslocationsinAML:DetectionandPrognostic
Significance................................................ 41
NallasivamPalanisamy
ChromosomalDeletionsinAML................................ 59
LalithaNagarajan
GenesPredictiveofOutcomeandNovelMolecularClassification
SchemesinAdultAcuteMyeloidLeukemia........................ 67
RoelG.W.VerhaakandPeterJ.M.Valk
ReceptorTyrosineKinaseAlterationsinAML–BiologyandTherapy... 85
DerekL.StirewaltandSoheilMeshinchi
Lineage-SpecificTranscriptionFactorAberrationsinAML........... 109
BeatriceU.MuellerandThomasPabst
ProleukemicRUNX1andCBFbMutationsinthePathogenesis
ofAcuteLeukemia........................................... 127
MichaelE.EngelandScottW.Hiebert
AcuteMyeloidLeukemiawithMutatedNucleophosmin(NPM1):
Molecular,Pathological,andClinicalFeatures..................... 149
BrunangeloFalini
MicroRNAs:NewPlayersinAMLPathogenesis ................... 169
MilenaS.Nicoloso,BhartiJasra,andGeorgeA.Calin
v
vi Contents
MurineModelsofHumanAcuteMyeloidLeukemia................. 183
JulieM.FortierandTimothyA.Graubert
ApoptosisinLeukemias:RegulationandTherapeuticTargeting........ 197
IsmaelSamudio,MarinaKonopleva,BingCarter,
andMichaelAndreeff
AcutePromyelocyticLeukemia:AParadigmforDifferentiation
Therapy................................................... 219
DavidGrimwade,AnitaR.Mistry,EllenSolomon,
andFabienGuidez
ImmunotherapyofAML ...................................... 237
GheathAlatrashandJeffreyJ.Molldrem
TherapyofAcuteMyelogenousLeukemiainAdults ................. 257
GautamBorthakurandElihu E. Estey
SubjectIndex............................................... 273
Contributors
GheathAlatrash,DO,PhD DivisionofCancerMedicine,UniversityofTexas
MDAndersonCancerCenter,Houston,TX,USA
MichaelAndreeff,MD,PhD DepartmentofBloodandMarrow
Transplantation,UniversityofTexasMDAndersonCancerCenter,Houston,
TX,USA,[email protected]
GautamBorthakur,MD DepartmentofLeukemia,TheUniversityofTexas
MDAndersonCancerCenter,Houston,TX,USA,
[email protected]
GeorgeA.Calin,MD,PhD DepartmentsofExperimentalTherapeuticsand
Cancer Genetics, The University of Texas MD Anderson Cancer Center,
Houston,TX,USA,[email protected]
BingCarter,PhD SectionofMolecularHematologyandTherapy,
DepartmentofStemCellTransplantationandCellular
Therapy,TheUniversityofTexasMDAndersonCancerCenter,
Houston,TX,USA
MichaelE.Engel,MD,PhD DivisionofPediatricHematology/Oncology,
DepartmentofPediatrics,MonroeCarellJr.Children’sHospitalatVanderbilt,
Vanderbilt-IngramCancerCenter,Nashville,TN,USA,
[email protected]
ElihuE.Estey,MD DepartmentofLeukemia,TheUniversityofTexasMD
AndersonCancerCenter,Houston,TX,USA
ZeevEstrov,MD DepartmentofLeukemia,UniversityofTexasMD
AndersonCancerCenter,Houston,TX,USA,[email protected]
BrunangeloFalini,MD InstituteofHematology,UniversityofPerugia,
Perugia,Italy,[email protected]
JulieM.Fortier,MD DivisionofOncology,StemCellBiologySection,
WashingtonUniversitySchoolofMedicine,St.Louis,MO,USA
vii
viii Contributors
TimothyA.Graubert,MD DivisionofOncology,StemCellBiologySection,
WashingtonUniversitySchoolofMedicine,St.Louis,MO,USA,
[email protected]
DavidGrimwade,MD,PhD DepartmentofMedicalandMolecularGenetics,
King’sCollegeLondonSchoolofMedicine,London,UK,
[email protected]
FabienGuidez,PhD DepartmentofMedicalandMolecularGenetics,King’s
CollegeLondonSchoolofMedicine,London,UK
ScottW.Hiebert,PhD DivisionofPediatricHematology/Oncology,
DepartmentofPediatrics,MonroeCarellJr.Children’sHospitalatVanderbilt,
Vanderbilt-IngramCancerCenter,Nashville,TN,USA
Jean-PierreJ.Issa,MD DepartmentofLeukemia,UniversityofTexasMD
AndersonCancerCenter,Houston,TX,USA,[email protected]
BhartiJasra,MD DepartmentsofExperimentalTherapeuticsandCancer
Genetics,TheUniversityofTexasMDAndersonCancerCenter,Houston,TX,USA
MarinaKonopleva,MD,PhD SectionofMolecularHematologyandTherapy,
DepartmentofLeukemia,TheUniversityofTexasMDAndersonCancer
Center,Houston,TX,USA
SoheilMeshinchi,MD,PhD ClinicalResearchDivision,FredHutchinson
CancerResearchCenter,Seattle,WA,USA
AnitaR.Mistry,PhD DepartmentofMedicalandMolecularGenetics,King’s
CollegeLondonSchoolofMedicine,London,UK
JeffreyJ.Molldrem,MD DepartmentofStemCellTransplantationand
CellularTherapy,UniversityofTexasMDAndersonCancerCenter,Houston,
TX,USA,[email protected]
BeatriceU.Mueller,MD DepartmentofInternalMedicine,University
Hospital,Bern,Switzerland,[email protected]
LalithaNagarajan,PhD DepartmentofMolecularGenetics,Universityof
TexasMDAndersonCancerCenter,Houston,TX,USA,
[email protected]
MilenaS.Nicoloso,MD DepartmentsofExperimentalTherapeuticsand
CancerGenetics,TheUniversityofTexasMDAndersonCancerCenter,
Houston,TX,USA
YasuhiroOki,MD DepartmentofLeukemia,UniversityofTexasMD
AndersonCancerCenter,Houston,TX,USA
ThomasPabst,MD DepartmentofOncology,UniversityHospital,Bern,
Switzerland
Contributors ix
NallasivamPalanisamy,PhD MichiganCenterforTranslationalPathology,
UniversityofMichiganHealthSystem,AnnArbor,MI,USA,
[email protected]
IsmaelSamudio,PhD SectionofMolecularHematologyandTherapy,
DepartmentofStemCellTransplantationandCellularTherapy,The
UniversityofTexasMDAndersonCancerCenter,Houston,TX,USA
EllenSolomon,PhD DepartmentofMedicalandMolecularGenetics,King’s
CollegeLondonSchoolofMedicine,London,UK
DerekL.Stirewalt,MD ClinicalResearchDivision,FredHutchinsonCancer
ResearchCenter,Seattle,WA,USA,[email protected]
PeterJ.M.Valk,PhD DepartmentofHematology,ErasmusUniversity
MedicalCenterRotterdam,Rotterdam,TheNetherlands,
[email protected]
RoelG.W.Verhaak,PhD DepartmentofHematology,ErasmusUniversity
MedicalCenterRotterdam,Rotterdam,TheNetherlands
The Leukemia Stem Cell
ZeevEstrov
Introduction and Historical Perspective
In a meeting held in the Charite´ Hospital in Berlin in 1909, Alexander Max-
imowpostulatedthatallcirculatingbloodcellsarisefromasinglelymphocyte-
like cell [68]. An almost identical hypothesis was proposed by Artur Pappen-
heim in 1917 [78]. This hypothesis was tested years later by numerous
investigatorswhodemonstratedthatallhematopoieticcellsarisefromasingle
hematopoietic stem cell (HSC) [54, 75, 90, 116]. Our knowledge of the leuke-
mogenicprocesshasbenefitedfromhematopoiesisresearch.Identificationand
characterization of the HSC led to the theory that leukemia is a stem cell
disease,i.e.,thatleukemiaarisesfromaneoplasticHSC.
Asfarasweknow,leukemiahasalwaysexisted.Thefirstpatientreportedto
exhibitsymptomsmostlikelyattributabletochroniclymphocyticleukemiawas
a 63-year-old Parisian lemonade salesman named Monsieur Vernis [108]. At
firsttherewasnotmuchinterestinthisdisease,andArmandVelpeau’sreport
drewlittleattention.However,withinafewyears,otherreportsfollowed.The
first cases of chronic myelogenous leukemia (CML) were reported by Donne
and Craigie [30, 25], and the clinical characteristics of several patients with
differentformsofleukemiawerepublishedbyJohnHughesBennett[5–9],who
first used the term ‘‘leucocythemia.’’ The word ‘leuka¨mie’ was coined by
RudolphVirchowwhobythenhaddescribedseveralpatientswiththisdisease
[110–113].Several decades passed beforethemorphological features ofleuke-
miacellsweredefinedandthepathophysiologyofleukemiadeciphered.
The stem cell concept has been applied to non-hematopoietic tissues.
Embryonic stem cells and non-hematopoietic, tissue-specific stem cells have
been isolated, characterized, and extensively studied [60]. Cells isolated from
embryonic tissue, gametes, and fertilized eggs have been found to have
Z.Estrov(*)
TheDepartmentofLeukemia,TheUniversityofTexasMD,AndersonCancerCenter,
Houston,TX,USA
e-mail:[email protected]
L.Nagarajan(ed.),AcuteMyelogenousLeukemia, 1
CancerTreatmentandResearch145,DOI10.1007/978-0-387-69259-3_1,
(cid:2)SpringerScienceþBusinessMedia,LLC2010
