Targeted treatment options for paediatric B-cell precursor acute lymphoblastic leukaemia patients with constitutional or somatic chromosome 21 alterations

Naomi Michels; Femke M. Hormann; Aurélie Boeree; Edwin Sonneveld; Anthony V. Moorman; Gabriele Escherich; Rosemary Sutton; H. Berna Beverloo; Rob Pieters; C. Michel Zwaan; Monique L. den Boer; Judith M. Boer

doi:10.1016/j.ejcped.2023.100140

Targeted treatment options for paediatric B-cell precursor acute lymphoblastic leukaemia patients with constitutional or somatic chromosome 21 alterations

Naomi Michels, Femke M. Hormann, Aurélie Boeree, Edwin Sonneveld, Anthony V. Moorman, Gabriele Escherich, Rosemary Sutton, H. Berna Beverloo, Rob Pieters, C. Michel Zwaan, Monique L. den Boer, Judith M. Boer^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background:

Chromosome 21 is affected in ∼60% of paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients and includes somatic and constitutional gains, intrachromosomal amplification of chromosome 21 (iAMP21), and the translocation t(12;21) resulting in the ETV6::RUNX1 gene fusion.

Methods:

Since these numeric and structural chromosome 21 alterations are not targetable, we studied the type and frequency of yet-proven targetable events co-occurring with chromosome 21 alterations.

Results:

Among 307 primary paediatric BCP-ALL cases, JAK/STAT pathway lesions were most frequent in patients with constitutional gain of chromosome 21 (Down syndrome ALL; 35/71, 49%) and iAMP21 (9/22, 41%). RAS pathway lesions were most frequent in high hyperdiploidy (62/108, 57%) and FLT3 lesions were most frequent in iAMP21 (7/22, 32%). Virtually all cases expressed CD19 and CD22 at the cell surface. Positivity for CD20 surface expression ranged from 67% in iAMP21 (8/12) to 20% in ETV6::RUNX1 (26/129).

Conclusion:

Activated JAK/STAT, RAS or FLT3 signalling, and CD marker surface expression may provide targetable treatment options for the majority of chromosome 21-altered BCP-ALL cases.

Original language	English
Article number	100140
Journal	EJC Paediatric Oncology
Volume	3
DOIs	https://doi.org/10.1016/j.ejcped.2023.100140
Publication status	Published - Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

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Targeted treatment options for paediatric B-cell precursor acute lymphoblastic leukaemia patients with constitutional or somatic chromosome 21 alterationsFinal published version, 6.25 MBLicence: CC BY-NC-ND

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Michels, N., Hormann, F. M., Boeree, A., Sonneveld, E., Moorman, A. V., Escherich, G., Sutton, R., Beverloo, H. B., Pieters, R., Zwaan, C. M., den Boer, M. L., & Boer, J. M. (2024). Targeted treatment options for paediatric B-cell precursor acute lymphoblastic leukaemia patients with constitutional or somatic chromosome 21 alterations. EJC Paediatric Oncology, 3, Article 100140. https://doi.org/10.1016/j.ejcped.2023.100140

@article{b91dcd1128704e459da0190991983572,

title = "Targeted treatment options for paediatric B-cell precursor acute lymphoblastic leukaemia patients with constitutional or somatic chromosome 21 alterations",

abstract = "Background: Chromosome 21 is affected in ∼60% of paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients and includes somatic and constitutional gains, intrachromosomal amplification of chromosome 21 (iAMP21), and the translocation t(12;21) resulting in the ETV6::RUNX1 gene fusion. Methods: Since these numeric and structural chromosome 21 alterations are not targetable, we studied the type and frequency of yet-proven targetable events co-occurring with chromosome 21 alterations.Results: Among 307 primary paediatric BCP-ALL cases, JAK/STAT pathway lesions were most frequent in patients with constitutional gain of chromosome 21 (Down syndrome ALL; 35/71, 49%) and iAMP21 (9/22, 41%). RAS pathway lesions were most frequent in high hyperdiploidy (62/108, 57%) and FLT3 lesions were most frequent in iAMP21 (7/22, 32%). Virtually all cases expressed CD19 and CD22 at the cell surface. Positivity for CD20 surface expression ranged from 67% in iAMP21 (8/12) to 20% in ETV6::RUNX1 (26/129). Conclusion: Activated JAK/STAT, RAS or FLT3 signalling, and CD marker surface expression may provide targetable treatment options for the majority of chromosome 21-altered BCP-ALL cases.",

author = "Naomi Michels and Hormann, {Femke M.} and Aur{\'e}lie Boeree and Edwin Sonneveld and Moorman, {Anthony V.} and Gabriele Escherich and Rosemary Sutton and Beverloo, {H. Berna} and Rob Pieters and Zwaan, {C. Michel} and {den Boer}, {Monique L.} and Boer, {Judith M.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = jun,

doi = "10.1016/j.ejcped.2023.100140",

language = "English",

volume = "3",

journal = "EJC Paediatric Oncology",

issn = "2772-610X",

publisher = "Elsevier",

}

Michels, N, Hormann, FM, Boeree, A, Sonneveld, E, Moorman, AV, Escherich, G, Sutton, R, Beverloo, HB, Pieters, R, Zwaan, CM, den Boer, ML & Boer, JM 2024, 'Targeted treatment options for paediatric B-cell precursor acute lymphoblastic leukaemia patients with constitutional or somatic chromosome 21 alterations', EJC Paediatric Oncology, vol. 3, 100140. https://doi.org/10.1016/j.ejcped.2023.100140

TY - JOUR

T1 - Targeted treatment options for paediatric B-cell precursor acute lymphoblastic leukaemia patients with constitutional or somatic chromosome 21 alterations

AU - Michels, Naomi

AU - Hormann, Femke M.

AU - Boeree, Aurélie

AU - Sonneveld, Edwin

AU - Moorman, Anthony V.

AU - Escherich, Gabriele

AU - Sutton, Rosemary

AU - Beverloo, H. Berna

AU - Pieters, Rob

AU - Zwaan, C. Michel

AU - den Boer, Monique L.

AU - Boer, Judith M.

PY - 2024/6

Y1 - 2024/6

N2 - Background: Chromosome 21 is affected in ∼60% of paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients and includes somatic and constitutional gains, intrachromosomal amplification of chromosome 21 (iAMP21), and the translocation t(12;21) resulting in the ETV6::RUNX1 gene fusion. Methods: Since these numeric and structural chromosome 21 alterations are not targetable, we studied the type and frequency of yet-proven targetable events co-occurring with chromosome 21 alterations.Results: Among 307 primary paediatric BCP-ALL cases, JAK/STAT pathway lesions were most frequent in patients with constitutional gain of chromosome 21 (Down syndrome ALL; 35/71, 49%) and iAMP21 (9/22, 41%). RAS pathway lesions were most frequent in high hyperdiploidy (62/108, 57%) and FLT3 lesions were most frequent in iAMP21 (7/22, 32%). Virtually all cases expressed CD19 and CD22 at the cell surface. Positivity for CD20 surface expression ranged from 67% in iAMP21 (8/12) to 20% in ETV6::RUNX1 (26/129). Conclusion: Activated JAK/STAT, RAS or FLT3 signalling, and CD marker surface expression may provide targetable treatment options for the majority of chromosome 21-altered BCP-ALL cases.

AB - Background: Chromosome 21 is affected in ∼60% of paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients and includes somatic and constitutional gains, intrachromosomal amplification of chromosome 21 (iAMP21), and the translocation t(12;21) resulting in the ETV6::RUNX1 gene fusion. Methods: Since these numeric and structural chromosome 21 alterations are not targetable, we studied the type and frequency of yet-proven targetable events co-occurring with chromosome 21 alterations.Results: Among 307 primary paediatric BCP-ALL cases, JAK/STAT pathway lesions were most frequent in patients with constitutional gain of chromosome 21 (Down syndrome ALL; 35/71, 49%) and iAMP21 (9/22, 41%). RAS pathway lesions were most frequent in high hyperdiploidy (62/108, 57%) and FLT3 lesions were most frequent in iAMP21 (7/22, 32%). Virtually all cases expressed CD19 and CD22 at the cell surface. Positivity for CD20 surface expression ranged from 67% in iAMP21 (8/12) to 20% in ETV6::RUNX1 (26/129). Conclusion: Activated JAK/STAT, RAS or FLT3 signalling, and CD marker surface expression may provide targetable treatment options for the majority of chromosome 21-altered BCP-ALL cases.

UR - http://www.scopus.com/inward/record.url?scp=85190422186&partnerID=8YFLogxK

U2 - 10.1016/j.ejcped.2023.100140

DO - 10.1016/j.ejcped.2023.100140

M3 - Article

AN - SCOPUS:85190422186

SN - 2772-610X

VL - 3

JO - EJC Paediatric Oncology

JF - EJC Paediatric Oncology

M1 - 100140

ER -

Targeted treatment options for paediatric B-cell precursor acute lymphoblastic leukaemia patients with constitutional or somatic chromosome 21 alterations

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