Molecular Characterization of Translocation(6;9) in Acute Nonlymphocytic Leukemia - Proefschrift

Sep 10, 2026

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Doctoral thesis describing the molecular characterization of the t(6;9) chromosomal translocation in acute nonlymphocytic leukemia. The work analyzes hematopoiesis and leukemogenesis, summarizes known genes and regulatory pathways, and develops a framework for understanding multistep disease progression. It focuses on clinical, cytogenetic, and morphological aspects of t(6;9) leukemia and investigates how the translocation rearranges two genes to produce specific fusion transcripts, enabling subtype-restricted gene expression.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages172

Reading Time7 h 13 min

AccessFree to download

CHAPTER 1 HEMATOPOIESIS AND LEUKEMIA

1.1 Normal hematopoiesis

1.2 Leukemogenesis

1.3 Characterization of genes involved in specific chromosomal aberrations in human leukemia

1.4 Leukemogenesis is a multistep process

1.5 References

CHAPTER 2

2.1 Clinical, cytogenetic and morphological aspects of t(6;9) acute nonlymphocytic leukemia

2.2 The human pim-1 gene is not directly activated by the translocation (6;9)

2.3 The (6;9) chromosome translocation leads to aberrant transcription of a target gene on 9q34

2.4 The translocation (6;9) results in gene fusion dek and can

2.5 The translocation (6;9)(p23;q34) shows consistent rearrangement of two genes

2.6 Can may be activated by fusion of its 3' half to different genes

2.7 Characterization of the translocation breakpoint sequences

CHAPTER 3 DISCUSSION

3.1 DEK-CAN and hematopoiesis

3.2 Future directions

SUMMARY

SAMENVATTING

CURRICULUM VITAE

PUBLICATIONS

NAWOORD

# MOLECULAR CHARACTERIZATION OF TRANSLOCATION(6;9)IN ACUTE NONLYMPHOCYTIC LEUKEMIA MOLEKULAIRE KARAKTERISATIE VAN TRANSLOCATIE(6;9)IN ACUTE NIETLYMFOCYTAIRE LEUKEMIE PROEFSCHRIFT ter verkrijging van de graad van doctoraan de Erasmus Universiteit Rotterdamop gezag van de Rector MagnificusProf.Dr.C.J.Rijnvosen volgens besluit van het College van Dekanen. De openbare verdediging zal plaats vinden opwoensdag 10 juni 1992 om 15.45 uur door Maartje Maria von Linderngeboren te Krimpen aan de Lek PROMOTIECOMMISSIE Promotor: Prof.Dr.D.Bootsma Overige leden:Prof.Dr.A.J.van der EBProf.Dr.A.HagemeijerProf.Dr.B.Löwenberg Co-promotor: Dr.G.C.Grosveld 叶 Printed by:Haveka B.V.,Alblasserdam,The Netherlands. Dit proefschrift is bewerkt binnen de vakgroep Celbiologie en Genetica van deFaculteit der geneeskunde en gezondheidswetenschappen van de ErasmusUniversiteit Rotterdam.De Nederlandse Kankerbestrijding(Koningin WilhelminaFonds)heeft het onderzoek financieel gesteund en heeft ook bijgedragen aan dedrukkosten van dit proefschrift. ……ours are”the two experiences of adult life”of whichPavese spoke,success and failure,to kill the white whale orwreck the ship;one should not surrender to incomprehensiblematter,one must not just sit down.We are here for this -tomake mistakes and to correct ourselves,to stand the blowsand hand them out.We must never feel disarmed;nature isimmense and complex,but it is not impermeable to theintelligence;we must circle around it,pierce and probe it,lookfor the opening or make it. Primo Levi,The Periodic Table aan allen die hun oprechte belangstellingvoor het hierbeschreven werk hebben getoond Omslag: Relief op de voorgevel van de dom van Modenavoorstellende het offer van Kain en Abel en de doodslagvan Abel.Beeldhouwer:Wiligelmo,begin 12°eeuw. ## CHAPTER 1HEMATOPOIESIS AND LEUKEMIA 1.1 Normal hematopoiesis13 1.2 Leukemogenesis 15 ## 1.3Characterization of genes involved in specific 17chromosomal aberrations in human leukemia 1.3.1 Ligands and receptors1711-3,tan-1 1.3.2 Signalling pathway19bcr-abl 1.3.3 Cell cycle regulation21bc/-1,bc/-3 1.3.4 Transcription regulation23bHLH genes:myc,scl/tal,Iyl,E2A-pbxHomeobox genes:E2A-pbx,HOX-11Rhombotins Steroid hormone receptor family:pml-RARaNFkB:rel-nrg,Iyt-10 32 1.3.5 Apoptosis bc/-2 ## 1.4 Leukemogenesis is a multistep process33 1.4.1 Enlargement of a susceptible compartment 34 1.4.2 Mutations involved in progression35 ## 1.5 References 37 2.1 (Clinical,cytogenetic and morphological51aspects of t(6;9)acute nonlymphocyticleukemia 2.2The human pim-1 gene is not directly57activated by the translocation(6;9)in acutenoniymphocytic leukemia Marieke von Lindern,Ton van Agthoven,AnneHagemeijer,Henk Adriaansen &Gerard GrosveldOncogene,4,75-79 2.3 The(6;9)chromosome translocation,63associated with a specific subtype of acutenonlymphocytic leukemia,leads to aberranttranscription of a target gene on 9q34Marieke von Lindern,Annemarie Poustka,HansLerach &Gerard GrosveldMolecular and Cellular Biology,10,4016-4026 2.4The translocation (6;9),associated with a75specific subtype of acute myeloid leukemiaresults in the fusion of two genes,dek andcan,and the expression of a chimeric,leukemia specific dek-can mRNA Marieke von Lindern,Maarten Fornerod,Sjozèf vanBaal,Martine Jaegle,Ton de Wit,Arjan Buijs &Gerard GrosveldMolecular and Cellular Biology,12,in press ## 2.5The translocation(6;9)(p23;q34)shows consistent rearrangement of two genes anddefines a myeloproliferative disorder withspecific clinical features D.Soekarman,M.von Lindern,S.Daenen,B.deJong,C.Fonatsch,B.Heinze,C.R.Bartram,A.Hagemeijer &G.GrosveldBlood,in press 2.6Can,a putative oncogene associated withmyeloid leukemogenesis,may be activatedby fusion of its 3'half to different genes:characterization of the set gene Marieke von Lindern,Sjozef van Baal,Joop Wiegant,Ton Raap,Anne Hagemeijer &Gerard GrosveldSubmitted for publication 2.7Characteri

FAQs

What is the main focus of this doctoral thesis?

The thesis focuses on the molecular characterization of the t(6;9) translocation in acute nonlymphocytic leukemia and how it affects gene rearrangements and expression.

Which biological processes are covered alongside the t(6;9) translocation?

It covers hematopoiesis and leukemogenesis, including pathways such as transcription regulation and apoptosis, and frames leukemogenesis as a multistep process.

What is established about gene fusion events in t(6;9) leukemia?

The document reports that the t(6;9) translocation leads to fusion of specific genes and expression of corresponding chimeric leukemia-specific transcripts.

Sep 10, 2026

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