Table Of ContentPrinciples and Practice
For furthervolumes:
http://www.springer.com/series/3580
Michał Witt Małgorzata Dawidowska
•
Tomasz Szczepan´ski
Editors
Molecular Aspects
of Hematologic
Malignancies
Diagnostic Tools and Clinical Applications
123
Editors
MichałWitt Małgorzata Dawidowska
International InstituteofMolecular Department of Molecular
and Cell Biology and Clinical Genetics
Warsaw Instituteof Human Genetics
Poland PolishAcademy ofSciences
Poznan´
and Poland
Department of Molecular Tomasz Szczepan´ski
and Clinical Genetics Department of PediatricHematology
Instituteof Human Genetics and Oncology
PolishAcademy ofSciences Medical University ofSilesia
Poznan´ Zabrze
Poland Poland
ISSN 1866-914X ISSN 1866-9158 (electronic)
ISBN 978-3-642-29466-2 ISBN 978-3-642-29467-9 (eBook)
DOI 10.1007/978-3-642-29467-9
SpringerHeidelbergNewYorkDordrechtLondon
LibraryofCongressControlNumber:2012940269
BasedinpartonthePolishlanguageedition:HematologiaMolekularna:patogeneza,patomechanizmyi
metody badawcze (ISBN 978-83-7314-119-3) (cid:2) Mie˛dzynarodowy Instytut Biologii Molekularnej i
Komórkowej,Warszawa2009.Allrightsreserved
(cid:2)Springer-VerlagBerlinHeidelberg2012
Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,
recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor
informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar
methodology now known or hereafter developed. Exempted from this legal reservation are brief
excerpts in connection with reviews or scholarly analysis or material supplied specifically for the
purposeofbeingenteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthe
work. Duplication of this publication or parts thereof is permitted only under the provisions of
theCopyrightLawofthePublisher’slocation,initscurrentversion,andpermissionforusemustalways
beobtainedfromSpringer.PermissionsforusemaybeobtainedthroughRightsLinkattheCopyright
ClearanceCenter.ViolationsareliabletoprosecutionundertherespectiveCopyrightLaw.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt
fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse.
While the advice and information in this book are believed to be true and accurate at the date of
publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor
anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with
respecttothematerialcontainedherein.
Printedonacid-freepaper
SpringerispartofSpringerScience+BusinessMedia(www.springer.com)
Preface
In recent years, there has been rapid development in molecular techniques,
allowing for precise and highly sensitive support of existing traditional methods
usedinhemato-oncology.Themostfrequentapplicationsofmoleculartechniques
in hematology include the identification of fusion genes resulting from chromo-
somaltranslocations,thedetectionofminimalresidualdisease,andtheanalysisof
chimerism following allogeneic hematopoietic stem cell transplantation. They
provideamethodologicalbasisforthewideningofhorizonsinhematologytoward
molecular problems, significantly modernizing basic research and allowing
fundamental questions to be tackled relating to hematopoietic stem cell biology,
the process of leukemogenesis, the response to therapy, etc. These methods are
also quickly becoming an essential component of modern diagnostic and thera-
peutic programs, revolutionizing clinical hemato-oncology toward more targeted
treatment.Atthemomentitishardtoimagineeffectivecareforpatientssubjected
to transplantation or to other forms of therapy consistent with modern criteria,
withoutthesystematicmonitoringofmolecularmarkersofdisease,givingusually
the most precise insight into the prognostic dilemma. This results in the wide-
spread creation of molecular hematology laboratories performing analyses
exclusively for the needs of relevant clinical units and creates the necessity for
collaboration between hematology clinical units and existing molecular genetic
labs. This entails understanding and collaboration between specialists from these
two quite different fields.
This monograph is neither another handbook of clinical hemato-oncology nor
an exclusive practical laboratory guide. Descriptions of selected hematological
malignancies (Part I), diagnostic procedures (Part II), and various aspects of
hematopoietic stem cell transplantation (Part III)focus on their molecular aspects
and in most of the cases correspond to a set of relevant laboratory protocols as
their counterparts (Part IV), giving, together with appropriate references to a
clinical realm, a bigger picture of the problem. Such a layout of the text proved
v
vi Preface
appropriate in our previous publications on the topic, while the smooth blend of
clinicalandmolecularproblemsperfectlymatchestherealitiesofmedicinetoday.
M. Witt
M. Dawidowska
T. Szczepan´ski
Contents
Part I Molecular Biology of Selected Hemato-oncologic Diseases
1 Molecular Biology of Acute Lymphoblastic Leukemia . . . . . . . . . 3
Małgorzata Dawidowska, Monika D. Kraszewska,
Katarzyna Derwich and Tomasz Szczepan´ski
2 Genetic Mechanisms and Molecular Markers
of Neoplastic Transformation in Acute Myeloid Leukemia. . . . . . 29
Agata A. Filip, Marta Libura, Sebastian Giebel and Olga Haus
3 Molecular Pathogenesis of Aggressive B-cell Lymphomas. . . . . . . 55
Przemysław Juszczyn´ski and Krzysztof Warzocha
4 Molecular Biology and Classification of Multiple Myeloma . . . . . 71
Anna Dmoszyn´ska and Norbert Grza˛s´ko
5 Chronic Lymphocytic Leukemia. . . . . . . . . . . . . . . . . . . . . . . . . 85
Anton W. Langerak and Yorick Sandberg
6 Molecular Biology of Chronic Myeloid Leukemia . . . . . . . . . . . . 103
Tomasz Sacha, Kajetana Foryciarz and Aleksander B. Skotnicki
7 Molecular Biology of Myelodysplastic Syndromes . . . . . . . . . . . . 117
Francesc Solé
8 Myeloproliferative Neoplasms. . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Andrzej Hellmann, Maria Bieniaszewska, Witold Prejzner
and Aleksandra Leszczyn´ska
vii
viii Contents
Part II Diagnostics and Monitoring of Therapy
of Hemato-oncologic Diseases
9 Flow Cytometric Immunophenotyping as Diagnostic Tool
of Hematopoietic Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Łukasz Se˛dek, Juan Flores-Montero, Joanna Bulsa, Susana Barrena,
Julia Almeida, Alberto Orfao and Tomasz Szczepan´ski
10 Cytogenetics in Hematology . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Olga Haus, Anna Poluha and Katarzyna Skonieczka
11 Monitoring of Minimal Residual Disease in Acute
Lymphoblastic Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Tomasz Szczepan´ski, Małgorzata Dawidowska
and Katarzyna Derwich
12 Gene Expression Profiling in Hematologic Malignancies . . . . . . . 199
Przemysław Juszczyn´ski, Bjoern Chapuy, Małgorzata Szczepaniak
and Krzysztof Warzocha
Part III Molecular Procedures Involved in Hematopoietic
Stem Cell Transplantation
13 Allogeneic Transplantation of Hematopoietic Stem Cells . . . . . . . 217
Jacek Wachowiak
14 Genetic Basis of Donor–Recipient Matching in Allogeneic
Transplantation of Hematopoietic Stem Cells . . . . . . . . . . . . . . . 237
Jacek Nowak and Jacek Wachowiak
15 Chimerism Following Allogeneic Transplantation
of Hematopoietic Stem Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
Małgorzata Dawidowska, Katarzyna Guz, Ewa Brojer,
Jacek Wachowiak and Michał Witt
16 Peritransplantation Monitoring of Minimal Residual Disease
in Acute Lymphoblastic Leukemia . . . . . . . . . . . . . . . . . . . . . . . 275
Małgorzata Dawidowska, Katarzyna Derwich
and Tomasz Szczepan´ski
17 Biobanks of Cellular Material. . . . . . . . . . . . . . . . . . . . . . . . . . . 285
Wiesław Wiktor-Je˛drzejczak and Elz_bieta Urbanowska
Contents ix
Part IV Molecular Diagnostic Protocols
18 Biobanking of Cellular Material. . . . . . . . . . . . . . . . . . . . . . . . . 299
Anna Poluha and Elz_bieta Urbanowska
19 Isolation of Mononuclear Cells from Human Blood and Bone
Marrow by Density Gradient Centrifugation. . . . . . . . . . . . . . . . 305
Małgorzata Dawidowska
20 Molecular Techniques Commonly Used in Hemato-oncology . . . . 309
Monika D. Kraszewska and Ewa Zie˛tkiewicz
21 Genetic Methods of HLA Typing . . . . . . . . . . . . . . . . . . . . . . . . 325
Jacek Nowak, Renata Mika-Witkowska and Elz_bieta Graczyk-Pol
22 Post-Transplant Chimerism Analysis Through STR-PCR
and RQ-PCR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341
Małgorzata Dawidowska, Katarzyna Guz, Agnieszka Orzin´ska,
Justyna Smolarczyk-Wodzyn´ska, Monika D. Kraszewska
and Michał Witt
23 Analysis of Minimal Residual Disease with the Use
of Rearrangements of Ig/TCR Genes Through RQ-PCR . . . . . . . 363
Małgorzata Dawidowska, Vincent H. J. van der Velden,
Michał Witt and Tomasz Szczepan´ski
24 Molecular Diagnostics of Acute Myeloblastic Leukemia. . . . . . . . 387
Marta Libura, Agata A. Filip and Olga Haus
25 Assessment of the Presence and the Level of BCR-ABL
Fusion Gene Expression and Mutational Status
in ABL Kinase Domain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411
Sylwia Czekalska, Magdalena Zawada and Izabela Florek
26 Studies of Rearrangements and Somatic Hypermutation
of IGHV Genes in Chronic Lymphocytic Leukemia. . . . . . . . . . . 429
Anton W. Langerak, Richard Rosenquist, Paolo Ghia,
Chrysoula Belessi, Kostas Stamatopoulos and Frederic Davi
27 Molecular Biology Methods in the Diagnosis
of Multiple Myeloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 443
Anna Dmoszyn´ska and Sylwia Chocholska
x Contents
28 Molecular Methods in Myeloproliferative Neoplasms. . . . . . . . . . 451
Aleksandra Leszczyn´ska, Witold Prejzner, Maria Bieniaszewska
and Andrzej Hellmann
29 Informed Consent for Participation in Research Project . . . . . . . 463
Małgorzata Dawidowska and Michał Witt
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 473
