Regenerating normal B-cell precursors during and after treatment of acute lymphoblastic leukaemia: implications for monitoring of minimal residual disease.
نویسندگان
چکیده
We studied 57 childhood acute lymphoblastic leukaemia (ALL) patients who remained in continuous complete remission after treatment according to the Dutch Childhood Leukaemia Study Group ALL-8 protocols. The patients were monitored at 18 time points during and after treatment [640 bone marrow (BM) and 600 blood samples] by use of cytomorphology and immunophenotyping for the expression of TdT, CD34, CD10 and CD19. Additionally, 60 BM follow-up samples from six patients were subjected to clonality assessment via heteroduplex polymerase chain reaction (PCR) analysis of immunoglobulin VH-JH gene rearrangements. We observed substantial expansions of normal precursor B cells in regenerating BM not only after maintenance therapy but also during treatment. At the end of the 2-week intervals after consolidation and reinduction treatment, B-cell-lineage regeneration was observed in BM with a large fraction of immature CD34+/TdT+ B cells. In contrast, in regenerating BM after cessation of maintenance treatment, the more mature CD19+/CD10+ B cells were significantly increased, but the fraction of immature CD34+/TdT+ B cells was essentially smaller. Blood samples showed a profound B-cell lymphopenia during treatment followed by a rapid normalization of blood B cells after treatment, with a substantial CD10+ fraction (10-30%). Heteroduplex PCR analysis confirmed the polyclonal origin of the expanded precursor B cells in regenerating BM. This information regarding the regeneration of BM is essential for the correct interpretation of minimal residual disease studies.
منابع مشابه
The relation between end of induction minimal residual disease and different risk factors in patients with acute lymphoblastic leukemia
Background: Malignant disorder with B or T stem cell basis leads to development and continuation of acute lymphoblastic leukemia (ALL) due to aggregation of blast cells in bone marrow. The environmental, genetic, and demographic factors may influence the disease relapse. The objective of this study was to assess the relation between end of induction minimal residual disease and different risk f...
متن کاملImmunophenotypic Subtyping of Leukemic Cells from Iranian Patients with Acute Lymphoblastic Leukaemia: Association to Disease Outcome
Background: Immunophenotypic characterization of the leukemic cells has been widely used as a tool for diagnosis, classification, stratification and prognosis of leukaemia. Objective: To investigate the immunophenotypic subtype profiles of Iranian patients with acute lymphoblastic leukemia (ALL) and its association to disease outcome. Methods: In this study, a total of 60 Iranian patients with ...
متن کاملFlow Cytometry Evaluation of Minimal Residual Disease in Acute Lymphoblastic Leukaemia Type B
Immunophenotyping has become essential to the diagnosis and the treatment management of acute lymphoblastic leukaemia (ALL). We prospectively studied minimal residual disease (MDR) in patients with B lineage ALL who achieved mCR remission. The initial series of patients consisted on 90 cases with B ALL. Sixty-Six patients had bone marrow samples adequate for MDR studies collected on day 35 of r...
متن کاملEvaluation of Relationship between Minimal Residual Disease (MRD) and Relapse in Childhood Acute Lymphoblastic Leukemia (ALL) Using Quantitative Fluorescent PCR
متن کامل
CD11b is a therapy resistance- and minimal residual disease-specific marker in precursor B-cell acute lymphoblastic leukemia.
A consistently increased mRNA expression of the adhesion receptor CD11b is a hallmark of the reported genomewide gene expression changes in precursor B-cell acute lymphoblastic leukemia (PBC-ALL) after 1 week of induction therapy. To investigate its clinical relevance, CD11b protein expression in leukemic blasts has been prospectively measured at diagnosis (159 patients) and during therapy (53 ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- British journal of haematology
دوره 110 1 شماره
صفحات -
تاریخ انتشار 2000