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Molecular Diagnostics

‘Evaluation of adverse prognostic gene alterations & MRD positivity in BCR::ABL1-like B-lineage acute lymphoblastic leukaemia patients, in a resource-constrained setting

Abstract

Background

Early detection of BCR::ABL1-like ALL could impact treatment management and improve the overall survival/outcome. BCR::ABL1-like ALL cases are characterised by diverse genetic alterations activating cytokine receptors and kinase signalling. Its detection is still an unmet need in low–middle-income countries due to the unavailability of a patented TLDA assay.

Methods

This study’s rationale is to identify BCR::ABL1-like ALLs using the PHi-RACE classifier, followed by the characterisation of underlying adverse genetic alterations in recurrent gene abnormalities negative (RGAneg) B-ALLs (n = 108).

Results

We identified 34.25% (37/108) BCR::ABL1-like ALLs using PHi-RACE classifier, characterised by TSLPR/CRLF2 expression (11.58%), IKZF1 (Δ4–7) deletion (18.9%) and chimeric gene fusions (34.61%). In overexpressed TSLPR/CRLF2 BCR::ABL1-like ALLs, we identified 33.33% (1/3) CRLF2::IGH and 33.33% (1/3) EPOR::IGH rearrangements with concomitant JAK2 mutation R683S (50%). We identified 18.91% CD13 (P = 0.02) and 27.02% CD33 (P = 0.05) aberrant myeloid markers positivity, which was significantly higher in BCR::ABL1-like ALLs compared to non-BCR::ABL1-like ALLs. MRD positivity was considerably higher (40% in BCR::ABL1-like vs. 19.29% in non-BCR::ABL1-like ALLs).

Conclusions

With this practical approach, we reported a high incidence of BCR::ABL1-like ALLs, and a lower frequency of CRLF2 alteration & associated CGFs. Recognising this entity, early at diagnosis is crucial to optimise personalised treatment strategies.

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Fig. 1
Fig. 2: Flowcytometric analysis.
Fig. 3: Scatter 2D plot acquired by Quanta Soft (1.7.4) software using CNV protocol.
Fig. 4: Flowcytometric analysis.
Fig. 5

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Data availability

All research data generated during this study are included in this research article.

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Acknowledgements

I sincerely thank the faculty of Haematology, technical staff, and clerical staff, project staff (Mrs Sonia) for providing valuable support for this study. I would like to extend my sincere thanks to Dr. Praveen (PGIMER), Dr Pramod Singh (PGIMER), Dr Mathew Li Arwood (Ann Roberts H. Lurie Children’s Hospital), and Dr Loretta S Li (Ann Roberts H. Lurie Children’s Hospital) for their valuable suggestions in this manuscript.

Funding

This research study was supported by the Intramural Grant provided by PGIMER, Chandigarh, India (No.71/2-Edu-16/937/18/03/2019). Dr. Dikshat Gopal Gupta received financial assistance from the Indian Council of Medical Education and Research (ICMR), New Delhi, India.

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DGG and NV designed the experiments and analysed the generated data; DGG, SS, JB and PB performed the experiments. DGG and NV wrote and prepared the manuscript; PM, AK and SV provided the adult B-ALL samples. SAA read, reviewed and helped us properly restructure the manuscript. All other authors read, provided intellectual comments, and approved the submitted manuscript.

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Correspondence to Neelam Varma.

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PGIMER constituted Institutional Ethics Committee had approved this research study (vide no. INT/IEC/2019/000611 dated March 19, 2019). In all, 2–3 ml of aspirated bone marrow (BM) or 3–5 ml of peripheral blood (PB) samples were collected, after obtaining the informed consent.

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Gupta, D.G., Varma, N., Sreedharanunni, S. et al. ‘Evaluation of adverse prognostic gene alterations & MRD positivity in BCR::ABL1-like B-lineage acute lymphoblastic leukaemia patients, in a resource-constrained setting. Br J Cancer 129, 143–152 (2023). https://doi.org/10.1038/s41416-023-02294-y

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