scholarly journals Modulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: Evidence for a drug-induced regulatory phenomenon. Results of the AIEOP-BFM-ALL-FLOW-MRD-Study Group

2010 ◽  
Vol 9999B ◽  
pp. NA-NA ◽  
Author(s):  
Michael N. Dworzak ◽  
Giuseppe Gaipa ◽  
Angela Schumich ◽  
Oscar Maglia ◽  
Richard Ratei ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Antigen Expression ◽  
Study Group ◽  
Cell Precursor ◽  
Drug Induced

CD20 up-Regulation in Childhood B-Cell Precursor Acute Lymphoblastic Leukemia during Induction Treatment Translates into Higher Rituximab-Sensitivity.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 906-906
Author(s):  
Andishe Attarbaschi ◽  
Angela Schumich ◽  
Georg Mann ◽  
Oskar A. Haas ◽  
Helmut Gadner ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Induction Therapy ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Remission Induction ◽  
Induction Treatment ◽  
Cell Precursor ◽  
The Impact

Abstract CD20 is expressed in about one half of childhood acute lymphoblastic leukemia (ALL) cases with B-cell precursor (BCP) origin. We recently observed that this phenotypic marker is further up-regulated in some patients during remission induction treatment containing corticosteroids for up to 5 weeks. To understand the impact of this phenomenon on the potential effectiveness of anti-CD20 immunotherapy (i.e., Rituximab), we studied 237 CD10-positive childhood BCP-ALL patients consecutively enrolled onto the trial AIEOP-BFM-ALL 2000. The analysis included the assessment of CD20 expression changes from diagnosis to the end of induction therapy and complement-induced cytotoxicity by CD20-targeting with Rituximab in-vitro. CD20-positivity significantly increased from diagnosis to the end of induction therapy with respect to the number of positive cases as well as to the levels of expression. After completion of induction therapy, one half of cases showed ≥ 90% CD20pos. leukemic cells, as opposed to 5% at diagnosis and 20% after 2 weeks of chemotherapy. Notably, up-regulation occurred in viable cells sustaining chemotherapy, most probably as a consequence of steroid-induced modulation of gene expression. Rituximab-cytotoxicity was significantly enhanced by CD20 up-regulation and depended on high expression levels. Importantly, CD20 up-regulation was frequent in high-risk patients (mainly poor prednisone responders), patients with high minimal residual disease levels at the end of induction therapy, and patients who suffered later from relapse, but not in TEL/AML1-positive cases. In conclusion, CD20 up-regulation is frequently induced in BCP-ALL during induction therapy and this translates into an acquired state of higher sensitivity to Rituximab.

scholarly journals Immunophenotypic characteristics of early T-cell precursor acute lymphoblastic leukemia

2019 ◽  
Vol 18 (2) ◽  
pp. 66-74
Author(s):  
A. S. Sharlai ◽  
O. I. Illarionova ◽  
Y. G. Fediukova ◽  
T. Yu. Verzhbitskaya ◽  
L. G. Fechina ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Molecular Genetic ◽  
Antigen Expression ◽  
Control Group ◽  
Study Group ◽  
Cell Precursor ◽  
Pediatric Hematology ◽  
National Medical

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized T-ymphoblastic leukemia subgroup with poor prognosis and high-risk of relapse. ETP-ALL subgroup is characterized by unique gene expression and particular cell surface markers profile. Nevertheless, this group cannot be easily detected due to its biological heterogeneity. The aim of the present study was to explore the immunophenotypic characteristics of early T-cell precursor acute lymphoblastic leukemia in ETP-ALL patient. The study group consisted of 64 patients with ETP-ALL. 380 patients with other variants of T-ALL were included to the control group. The antigen expression profile was assessed by multicolor flow cytometry. TI and TII immunological variants were detected in the group of patients with ETP-ALL. Cell markers expression level was determined in both groups. In the study group of ETP-ALL patients CD11a expression was more specific to TII-ALL, while CD33 expression – for TI-ALL. This study allowed to characterize group of patients with ETP-ALL and detected immunophenotypic heterogeneity. More interlaboratory studies are needed for understanding immunological and molecular genetic features ETP-ALL. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology.

The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group

Blood ◽  
2009 ◽  
Vol 113 (17) ◽  
pp. 4011-4015 ◽  
Author(s):  
Thomas Burmeister ◽  
Claus Meyer ◽  
Stefan Schwartz ◽  
Julia Hofmann ◽  
Mara Molkentin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Fusion Transcript ◽  
White Blood Count ◽  
Study Group ◽  
Cell Precursor ◽  
Long Distance ◽  
Diagnostic Laboratory ◽  
Chromosomal Breakpoints

Abstract MLL translocations in adult B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) are largely restricted to the immature CD10− immunophenotypes. MLL-AF4 is known to be the most frequent fusion transcript, but the exact frequencies of MLL aberrations in CD10− adult BCP-ALL are unknown. We present a genetic characterization of 184 BCR-ABL− CD10− adult ALL cases (156 cyIg−, 28 cyIg+) diagnosed between 2001 and 2007 at the central diagnostic laboratory of the GMALL study group. Patient samples were investigated by RT-PCR for MLL-AF4, MLL-ENL, and MLL-AF9 and by long-distance inverse polymerase chain reaction, thus also allowing the identification of unknown MLL fusion partners at the genomic level. MLL-AF4 was detected in 101 (54.9%) and MLL-ENL in 11 (6.0%) cases. In addition, rare MLL fusion genes were found: 2 MLL-TET1 cases, not previously reported in ALL, 1 MLL-AF9, 1 MLL-PTD, a novel MLL-ACTN4, and an MLL-11q23 fusion. Chromosomal breakpoints were determined in all 118 positive cases, revealing 2 major breakpoint cluster regions in the MLL gene. Characteristic features of MLL+ patients were significantly lower CD10 expression, expression of the NG2 antigen, a higher white blood count at diagnosis, and female sex. Proposals are made for diagnostic assessment. The clinical studies are registered at http://www.clinicaltrials.gov as NCT00199056 and NCT00198991.

scholarly journals p21WAF1 modulates drug-induced apoptosis and cell cycle arrest in B-cell precursor acute lymphoblastic leukemia

Cell Cycle ◽  
2015 ◽  
Vol 14 (22) ◽  
pp. 3602-3612 ◽  
Author(s):  
Carwyn Davies ◽  
Linda A Hogarth ◽  
Karen L Mackenzie ◽  
Andrew G Hall ◽  
Richard B Lock
Keyword(s):  
Cell Cycle ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Cell Cycle Arrest ◽  
Lymphoblastic Leukemia ◽  
Cell Precursor ◽  
Drug Induced ◽  
Cycle Arrest ◽  
Induced Apoptosis

Reappraisal of the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia.

1998 ◽  
Vol 16 (12) ◽  
pp. 3768-3773 ◽  
Author(s):  
C H Pui ◽  
J E Rubnitz ◽  
M L Hancock ◽  
J R Downing ◽  
S C Raimondi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Antigen Expression ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Cell Precursor ◽  
Childhood All ◽  
Mll Gene ◽  
Blast Cells

PURPOSE To reassess the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS We prospectively studied 334 newly diagnosed cases of this disease, using a comprehensive panel of antibodies that represented five myeloid cluster groups (CD13, CD14, CD15, CD33, and CD65). Blast cells were tested for ETV6 and MLL rearrangement using Southern blot analysis. RESULTS CD13 was expressed in 13.7% of cases, CD14 in 1%, CD15 in 6.6%, CD33 in 16%, and CD65 in 9.7%. Approximately one third of cases (31.4%) expressed one or more of these antigens (B-cell precursor, 31.9%; T-cell, 28.8%), while 10.5% expressed two or more (B-cell precursor, 11.3%; T-cell, 6.1%). Among the B-cell precursor leukemias, myeloid-associated antigen expression was significantly associated with a lack of hyperdiploidy and rearrangements of ETV6 or MLL gene. Most of the cases with MLL rearrangements (82%) expressed CD65, CD15, and CD33, either alone or in combination, whereas 48% of those with a rearranged ETV6 gene expressed CD13, CD33, or both. Myeloid-associated antigen expression did not correlate with event-free survival, whether the analysis was based on any of the five antigens in our panel or on the three more commonly tested antigens (CD13, CD33, and CD65). Importantly, this finding was not affected by exclusion of patients with ETV6 or MLL gene rearrangements. CONCLUSION Even though blast cell expression of myeloid-associated antigen expression shows significant associations with specific genetic abnormalities, it lacks prognostic value in childhood ALL.

Sign in / Sign up

Export Citation Format

Share Document