Childhood B Lineage Acute Lymphoblastic Leukemia Clonality Study by the Polymerase Chain Reaction

Scrideli, Carlos Alberto; Simões, Aguinaldo Luíz; Defavery, Ricardo; Bernardes, José Eduardo; Duarte, M; Tone, Luíz Gonzaga

doi:10.1097/00043426-199711000-00005

Cited by 18 publications

(9 citation statements)

References 41 publications

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“…24 Clonality was characterized by the presence of a band of the expected size in the homo/heteroduplex analysis on 12% polyacrylamide gel. The expected fragment sizes are: 80 to 120 bp for CDR 3 (IGH), 80 to 100 bp for TCRD, 170 to 210 bp for TCRG, [19][20][21]25 364 to 433 bp for IGK mix 1, and 175 to 443 bp for mix IGK mix 2. The samples analyzed on day 14 and day 28 of induction therapy were used at a DNA concentration of 500 ng/reaction and were considered to be positive when they presented the same migration pattern as the samples obtained at diagnosis and amplified in the same reaction for IGH, IGK and/or TCR rearrangements (see, for example, Figure 1).…”

Section: Minimal Residual Disease Determined By Polymerase Chain Reacmentioning

confidence: 99%

A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

Scrideli

Assumpção²,

Ganazza³

et al. 2009

Haematologica

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The online version of this article contains a supplementary appendix. BackgroundMinimal residual disease is an important independent prognostic factor in childhood acute lymphoblastic leukemia. The classical detection methods such as multiparameter flow cytometry and real-time quantitative polymerase chain reaction analysis are expensive, time-consuming and complex, and require considerable technical expertise. Design and MethodsWe analyzed 229 consecutive children with acute lymphoblastic leukemia treated according to the GBTLI-99 protocol at three different Brazilian centers. Minimal residual disease was analyzed in bone marrow samples at diagnosis and on days 14 and 28 by conventional homo/heteroduplex polymerase chain reaction using a simplified approach with consensus primers for IG and TCR gene rearrangements. ResultsAt least one marker was detected by polymerase chain reaction in 96.4% of the patients. By combining the minimal residual disease results obtained on days 14 and 28, three different prognostic groups were identified: minimal residual disease negative on days 14 and 28, positive on day 14/negative on day 28, and positive on both. Five-year event-free survival rates were 85%, 75.6%, and 27.8%, respectively (p<0.0001). The same pattern of stratification held true for the group of intensively treated children. When analyzed in other subgroups of patients such as those at standard and high risk at diagnosis, those with positive B-derived CD10, patients positive for the TEL/AML1 transcript, and patients in morphological remission on a day 28 marrow, the event-free survival rate was found to be significantly lower in patients with positive minimal residual disease on day 28. Multivariate analysis demonstrated that the detection of minimal residual disease on day 28 is the most significant prognostic factor. ConclusionsThis simplified strategy for detection of minimal residual disease was feasible, reproducible, cheaper and simpler when compared with other methods, and allowed powerful discrimination between children with acute lymphoblastic leukemia with a good and poor outcome.

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Section: Minimal Residual Disease Determined By Polymerase Chain Reacmentioning

confidence: 99%

A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

Scrideli

Assumpção²,

Ganazza³

et al. 2009

Haematologica

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“…Close to 80% of ALL cases are a result of clonal expansion of B-cell precursors and contain rearrangements in the heavy-chain immunoglobulin (IgH) gene. 2 In addition, crosslineage T-cell receptor (TCR) gene rearrangements frequently occur in B-cell precursor ALL: rearranged TCR ␤, TCR ␥, and TCR ␦ are found in 35%, 55%, and 90% of cases, respectively. 1 Thus polymerase chain reaction (PCR) analysis of immunoreceptor gene rearrangements can be used for clonality studies in lymphoid leukemias.…”

Section: Introductionmentioning

confidence: 99%

Detection of leukemic cells in the CD34+CD38− bone marrow progenitor population in children with acute lymphoblastic leukemia

George

Franklin

Kerkof

et al. 2001

Blood

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Successful autologous hematopoietic stem cell (HSC) transplantation in childhood acute lymphoblastic leukemia (ALL) requires the ability to either selectively kill the leukemia cells or separate normal from leukemic HSC. Based on previous studies showing that more than 95% of childhood B-lineage ALL express CD38, this study evaluated whether normal CD34 ؉ CD38 ؊ progenitors from children with B-lineage ALL could be isolated by flow cytometry. CD34 ؉ cells from bone marrow samples from 10 children with B-lineage ALL were isolated at day 28 of treatment, when clinical remission had been attained. The CD34 ؉ progenitor cells were flow cytometrically sorted into CD34 ؉ CD38 ؉ and CD34 ؉ CD38 ؊ populations. The absolute numbers of CD34 ؉ CD38 ؊ cells that could be isolated ranged from 401 to 6245. The cells were then analyzed for the presence of clonotypic rearrangements of the T-cell receptor (TCR) V␦2-D␦3 locus. Only patients whose diagnostic marrow had an informative TCR V␦2-D␦3 rearrangement were included in this study. Detection thresholds were typically 10 ؊4 to 10 ؊5 leukemic cells in normal marrow. In 6 of 10 samples analyzed, the sorted CD34 ؉ CD38 ؊ cells had no detectable V␦2-D␦3 rearrangements. In 4 cases, the clonotypic leukemic V␦2-D␦3 rearrangement was detected in the CD34 ؉ CD38 ؊ population, indicating that the putative normal HSC population also contained leukemic cells. The data indicate that although most childhood ALL cells express CD34 and CD38, leukemic cells are also frequently present in the CD34 ؉ CD38 ؊ population. Therefore, strategies to isolate and transplant normal HSC from children with ALL will require a more stringent definition of the normal HSC than the CD34 ؉ CD38 ؊ phenotype. (Blood. 2001;97:3925-3930)

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“…A majority of ALL cases involve the expansion of B-cell lymphoid progenitor cells (76). However, it has also been suggested that the expansion of T-cells as the origin of leukemia initiating cells in ALL (77).…”

Section: Origin Of Cancer Stem Cellsmentioning

confidence: 99%

Cancer stem cells - from initiation to elimination, how far have we reached? (Review)

Akhtar

Bussen²,

Scott³

2009

Int J Oncol

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Abstract. Cancer stem cells (CSCs) are rare tumor cells that have the potential to proliferate, self-renew and induce tumorigenesis. Over the past few years, CSCs have been isolated from several different tumors and when implanted into immune-deficient mice, generate tumors that are identical to the parental tumors. In this review, we summarize the current literature on CSCs, which suggests that since these cells have the ability to drive tumor formation, specifically targeting them may lead to more effective therapies against tumors.

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Childhood B Lineage Acute Lymphoblastic Leukemia Clonality Study by the Polymerase Chain Reaction

Abstract: PCR using CDR-3 and TCR delta primers can be used as an aid for B lineage ALL diagnosis and clonal evolution of theses disease.

Cited by 18 publications

References 41 publications

A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

Detection of leukemic cells in the CD34+CD38− bone marrow progenitor population in children with acute lymphoblastic leukemia

Cancer stem cells - from initiation to elimination, how far have we reached? (Review)

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