scholarly journals Lymphocytic progenitor cell origin and clonal evolution of human B- lineage acute lymphoblastic leukemia

Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 609-621 ◽  
Author(s):  
F Davi ◽  
C Gocke ◽  
S Smith ◽  
J Sklar
Keyword(s):  
Sequence Analysis ◽  
Nucleotide Sequence ◽  
Progenitor Cell ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Nucleotide Sequence Analysis ◽  
Chromosomal Marker ◽  
Gene Rearrangements ◽  
B Lineage

At presentation, bone marrow specimens from over 25% of B-lineage acute lymphoblastic leukemias (ALL) display more than two clonal rearrangements of immunoglobulin heavy chain (IgH) genes in Southern blot analyses. Nucleotide sequence analysis has shown predominantly different V(H)DJ(H) junctions among these genes, leading to the frequent description of such cases as oligoclonal leukemias. In the present study, we have analyzed the lgH genes from four patients whose leukemic cells contained different patterns of lgH gene rearrangements between presentation and relapse. Nucleotide sequence analysis of the lgH genes showed that three mechanisms could account for these differences: de novo V(H)DJ(H) rearrangement, V(H) to DJ(H) recombination, and V(H) replacement. In all cases, more than two totally different V(H)DJ(H) rearrangements appeared during evolution of the disease, formally consistent with the conclusion that these tumors were composed of apparently unrelated clones. However, the retention of some of the antigen receptor gene rearrangements, as well as the persistence of a chromosomal marker in two cases, indicated that these leukemias had a monoclonal origin. These findings support the hypothesis that some ALLs arise from a lymphoid progenitor cell at a stage of lymphocyte development before the onset of IgH gene rearrangement. These leukemic lymphocyte progenitors generate malignant daughter cells capable of an in vivo maturation that involves the completion of multiple different lgH rearrangements as well as the modification of preexisting rearrangements by V(H) to DJ(H) recombination or by a V(H) replacement.

scholarly journals Continuing rearrangement but absence of somatic hypermutation in immunoglobulin genes of human B cell precursor leukemia.

1988 ◽  
Vol 168 (1) ◽  
pp. 229-245 ◽  
Author(s):  
J Bird ◽  
N Galili ◽  
M Link ◽  
D Stites ◽  
J Sklar
Keyword(s):  
Sequence Analysis ◽  
B Cell ◽  
Heavy Chain ◽  
De Novo ◽  
Nucleotide Sequence Analysis ◽  
Cell Precursor ◽  
Cell Stage ◽  
V Region ◽  
B Lineage ◽  
Ig Heavy Chain

Southern blot analyses revealed that cells from nearly 30% of childhood B cell precursor acute lymphoblastic leukemias (ALLs) contained more than two rearranged, nongermline bands for Ig heavy chain genes. DNA corresponding to these bands was molecularly cloned from two cases which showed three and seven rearranged bands, respectively. Nucleotide sequence analysis of the cloned DNA demonstrated that each band represented different VDJ or DJ rearrangements. While the same DJ joints were shared by several rearrangements, different DJ joints were found in the majority of rearrangements, precluding V region substitution as an explanation for the multiplicity of heavy chain rearrangements in these leukemias. Most of the V region segments involved in these rearrangements were restricted to VH region families that have been shown previously to be preferentially rearranged in human fetal B lineage cells. Sequence analysis of multiple copies of the same VDJ rearrangements from different cells revealed no somatic mutation, a mechanism responsible for detection of extra rearranged Ig DNA bands in certain other B lineage tumors. The data suggest that in some cases of ALL Ig heavy chain genes begin and continue to rearrange de novo within the neoplastic B cell precursor populations derived from an original malignant cell transformed at a stem cell stage of differentiation.

Nucleotide sequence analysis of the BALB/c murine sarcoma virus transforming gene.

1985 ◽  
Vol 53 (3) ◽  
pp. 984-987 ◽  
Author(s):  
E P Reddy ◽  
D Lipman ◽  
P R Andersen ◽  
S R Tronick ◽  
S A Aaronson
Keyword(s):  
Sequence Analysis ◽  
Nucleotide Sequence ◽  
Nucleotide Sequence Analysis ◽  
Murine Sarcoma Virus ◽  
Sarcoma Virus ◽  
Murine Sarcoma ◽  
Transforming Gene

scholarly journals Six New Subgroup I Members of Japanese Cucumber Mosaic Virus as Determined by Nucleotide Sequence Analysis on RNA3's cDNAs.

1996 ◽  
Vol 62 (1) ◽  
pp. 40-44 ◽  
Author(s):  
Piyasak CHAUMPLUK ◽  
Yukiko SASAKI ◽  
Naoko NAKAJIMA ◽  
Hideaki NAGANO ◽  
Ikuo NAKAMURA ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Nucleotide Sequence ◽  
Cucumber Mosaic Virus ◽  
Mosaic Virus ◽  
Nucleotide Sequence Analysis

scholarly journals Nucleotide sequence analysis of a cDNA encoding human ubiquitin reveals that ubiquitin is synthesized as a precursor.

1985 ◽  
Vol 260 (12) ◽  
pp. 7609-7613 ◽  
Author(s):  
P K Lund ◽  
B M Moats-Staats ◽  
J G Simmons ◽  
E Hoyt ◽  
A J D'Ercole ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Nucleotide Sequence ◽  
Nucleotide Sequence Analysis ◽  
Human Ubiquitin

scholarly journals Unravelling the Sequential Interplay of Mutational Mechanisms during Clonal Evolution in Relapsed Pediatric Acute Lymphoblastic Leukemia

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 214
Author(s):  
Željko Antić ◽  
Stefan H. Lelieveld ◽  
Cédric G. van der Ham ◽  
Edwin Sonneveld ◽  
Peter M. Hoogerbrugge ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Leukemic Cells ◽  
Proliferative Potential ◽  
Disease Evolution ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
First Relapse ◽  
Mutational Processes

Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and is characterized by clonal heterogeneity. Genomic mutations can increase proliferative potential of leukemic cells and cause treatment resistance. However, mechanisms driving mutagenesis and clonal diversification in ALL are not fully understood. In this proof of principle study, we performed whole genome sequencing of two cases with multiple relapses in order to investigate whether groups of mutations separated in time show distinct mutational signatures. Based on mutation allele frequencies at diagnosis and subsequent relapses, we clustered mutations into groups and performed cluster-specific mutational profile analysis and de novo signature extraction. In patient 1, who experienced two relapses, the analysis unraveled a continuous interplay of aberrant activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) activity. The associated signatures SBS2 and SBS13 were present already at diagnosis, and although emerging mutations were lost in later relapses, the process remained active throughout disease evolution. Patient 2 had three relapses. We identified episodic mutational processes at diagnosis and first relapse leading to mutations resembling ultraviolet light-driven DNA damage, and thiopurine-associated damage at first relapse. In conclusion, our data shows that investigation of mutational processes in clusters separated in time may aid in understanding the mutational mechanisms and discovery of underlying causes.

scholarly journals Human acute leukemia cell line with the t(4;11) chromosomal rearrangement exhibits B lineage and monocytic characteristics

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 21-31 ◽  
Author(s):  
RC Stong ◽  
SJ Korsmeyer ◽  
JL Parkin ◽  
DC Arthur ◽  
JH Kersey
Keyword(s):  
Acute Leukemia ◽  
Cell Line ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Leukemic Cells ◽  
Leukemia Cell Line ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Immunoglobulin Gene ◽  
A Cell ◽  
B Lineage

Abstract A cell line, designated RS4;11, was established from the bone marrow of a patient in relapse with an acute leukemia that was characterized by the t(4;11) chromosomal abnormality. The cell line and the patient's fresh leukemic cells both had the t(4;11)(q21;q23) and an isochromosome for the long arm of No. 7. Morphologically, all cells were lymphoid in appearance. Ultrastructurally and cytochemically, approximately 30% of the cells possessed myeloid features. The cells were strongly positive for terminal deoxynucleotidyl transferase. They were HLA-DR positive and expressed surface antigens characteristic for B lineage cells, including those detected by anti-B4, BA-1, BA-2, and PI153/3. Immunoglobulin gene analysis revealed rearrangements of the heavy chain and kappa chain genes. The cells lacked the common acute lymphoblastic leukemia antigen and antigenic markers characteristic of T lineage cells. The cells reacted with the myeloid antibody 1G10 but not with other myeloid monoclonal antibodies. Treatment with 12-O-tetradecanoyl- phorbol-13-acetate induced a monocyte-like phenotype demonstrated by cytochemical, functional, immunologic, and electron microscopic studies. The expression of markers of both early lymphoid and early myeloid cells represents an unusual phenotype and suggests that RS4;11 represents a cell with dual lineage capabilities. To our knowledge, RS4;11 is the first cell line established from t(4;11)-associated acute leukemia.

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