New personalized test for an earlier and more accurate prediction of
cancer relapse

Date:
February 7, 2022
Source:
Elsevier
Summary:
Researchers have developed a new protocol for monitoring acute
lymphoblastic leukemia (ALL), the most common cancer in children,
to inform more effective treatment strategies and detect disease
recurrence.

The personalized mediator probe PCR (MP PCR) uses multiple genomic
cancer cell markers in a single assay and is simpler than current
techniques. It improves monitoring clonal tumor evolution to detect
a relapse sooner and avoid false negative results.



FULL STORY ========================================================================== Researchers have developed a new protocol for monitoring acute
lymphoblastic leukemia (ALL), the most common cancer in children,
to inform more effective treatment strategies and detect disease
recurrence. The personalized mediator probe PCR (MP PCR) uses multiple
genomic cancer cell markers in a single assay and is simpler than current techniques. It improves monitoring clonal tumor evolution to detect
a relapse sooner and avoid false negative results. Their protocol is
detailed in The Journal of Molecular Diagnostics, published by Elsevier.


==========================================================================
The survival rate for children with ALL has increased impressively to over
80% over the last several decades. However, the prognosis for children
whose cancer recurs remains unfavorable. Therefore, minimal residual
disease (MRD) monitoring is an important prognostic factor for treatment response and patient stratification. MRD monitoring uses highly sensitive real-time PCR to measure the amount of cancer cells among normal cells.

"MRD markers can disappear during treatment, which can lead to
false-negative results and poor decision-making in personalized
treatments," explains Principal investigator Cornelia Eckert,
PhD, Department of Pediatric Oncology/ Hematology, Charite' -- Universita"tsmedizin Berlin, German Cancer Consortium (DKTK) and German
Cancer Research Center (DKFZ). Consequently, monitoring at least two independent markers per patient is recommended. Dr. Eckert continues,
"The current gold standard EuroMRD consortium guidelines call for
amplification using singleplex real-time PCR quantification, making
testing additional markers more laborious and expensive. They also lead to
a higher consumption of patient material." To overcome these limitations,
Dr. Eckert and co-investigators established the personalized MP PCR,
an iterative workflow and guidelines for designing multiplex real-time
PCRs to monitor up to four MRD markers for ALL simultaneously in one
assay. When tested on DNA in bone marrow samples from patients with
ALL, the MP PCRs met the EuroMRD gold standard guidelines and level of sensitivity for clinical decision-making.

Co-investigator Michael Lehnert, PhD, Hahn-Schickard Freiburg, states, "Multiplexing can significantly improve personalized MRD monitoring
of patients, because a higher number of MRD markers per patient can be
analyzed at the same time. Even though these patient-specific sequences
of cancer cells only differ in a few DNA nucleotides from healthy
cells, our multiplex assay can still distinguish between these DNA
sequences. Therefore, a broader range of patient-specific sequences
can be included in the assay." The MRD-MP guidelines are simple and
may allow assay standardization across different laboratories. To
demonstrate the potential transfer of the duplex MP PCR into a routine diagnostic setting, the new assay was applied in a prospectively assessed patient case in comparison with the gold standard singleplex test. Both fulfilled the EuroMRD guidelines and led to a similar quantitative range
and sensitivity.

In order to deal with challenges inherent to multiplex PCR, the
researchers developed an efficient iterative workflow for PCR design
and optimization. DNA primer titration is only involved and extended if
the assay performance is not sufficient in the first step, so that the
number of iterations is minimized.

"There is a vast variety of DNA marker sequences unique to each leukemia,"
adds first author Elena Kipf, PhD, Hahn-Schickard Freiburg. "The
MRD-multiplex workflow provides a systematic and reliable way of effective MRD-MP PCR design and optimization and helps the standardization of
personal diagnostics." While their work demonstrates that multiplex
MP PCR has the potential to set a new standard in personalized MRD
monitoring, the researchers note it must be clinically validated in a representative cohort of ALL patients. "Cancer is a fatal disease from
which not every patient can be cured," Dr. Eckert stresses.

"After successful clinical validation, patients could benefit
from extended MRD monitoring, leading to more precise predictions
of therapy response and better patient stratification and outcomes." ========================================================================== Story Source: Materials provided by Elsevier. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Elena Kipf, Franziska Schlenker, Nadine Borst, Marion Fillies,
Renate
Kirschner-Schwabe, Roland Zengerle, Cornelia Eckert, Felix
von Stetten, Michael Lehnert. Advanced Minimal Residual Disease
Monitoring for Acute Lymphoblastic Leukemia with Multiplex Mediator
Probe PCR. The Journal of Molecular Diagnostics, 2022; 24 (1):
57 DOI: 10.1016/j.jmoldx.2021.10.001 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220207124835.htm

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