Classification of Hematogons and Neoplastic B Lymphoblasts through Computational Analysis of Immunophenotypic Flow Cytometry Data

Definitions

Mature B Lymphocyte - plays role in adaptive immunity , produced by hematopoietic stem cell (HSC) in the bone marrow

Hematogone - a normal immature B cell , undergoes lymphopoiesis to become a mature B lymphocyte

Neoplastic B Lymphoblast - an abnormal cell that originates from HSC that show an aberrant immunophenotype

B cell acute lymphoblastic leukemia ( B-ALL ) - a common childhood cancer that occurs due to neoplastic B lymphoblast proliferation

Minimal Residual Disease (MRD) - very small number of cancer cells ( in this case neoplastic B lymphoblast ) that remain in the body during or after treatment , an independent predictor for an increased risk of relapse in B-ALL

The Problem

Hematogons (HGs) are immature B lineage cells that show similar immunophenotypic characteristics to neoplastic B lymphoblasts

Hematogon overproduction ( can be seen in children and those who receive chemotherapy ) could be misinterpreted as B-ALL or MRD

Differentiating between these two entities is crucial for accurate B-ALL monitoring , but it is often challenging and , in many cases , cannot be reliably achieved

The Solution

Using supervised machine learning to determine the optimal linear combination of parameters for classifying these cell populations

What We Know

Aberrant antigen expression of neoplastic B lineage lymphoblasts:

(i) over expression of CD10 , CD34
(ii) under expression of CD38 , CD45
(iii) over/under expression of CD22
(iv) coexpression of CD20 , CD34
(v) cross lineage antigen expression

HG demonstrate consistent and reproducible antigen expression patterns during their development:

(i) Bright CD10 – ↓↓ as they mature
(ii) Bright CD 38 – may ↓ as they mature
(iii) Positive CD 34 – ↓↓ as they mature
(iv) Dim CD 45 – ↓ as they mature
(v) Negative CD20 – ↑ as they mature

Mature B cells are negative for CD34 , CD10 ; positive for CD20 , CD45 ; show variable patterns for CD38.

Flow Cytometry Analysis of Hematogons and Neoplastic B Lymphoblasts

Credit : https://www.cytometry.org/web/q_view.php?id=4&filter=Interpretation%20and%20Clinical%20Application

Collaboration

This project is funded by Scientific and Technological Research Council of Turkey (TÜBİTAK) 2209-A project support programme

https://tubitak.gov.tr/en/scholarships/degree-associate-degree/scholarship-programs/2209-research-project-support-programme-undergraduate-students

References

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