Volume 43, Issue 6 pp. 1531-1538
ORIGINAL ARTICLE

Mutational landscape of Juvenile Myelomonocytic Leukemia (JMML)—A real-world context

Shrinidhi Nathany

Shrinidhi Nathany

Department of Hematopathology, Advanced Centre for Treatment and Research in Cancer, Tata Memorial Centre, Mumbai, India

Homi Bhabha National Institute (HBNI), Mumbai, India

Search for more papers by this author
Gaurav Chatterjee

Gaurav Chatterjee

Department of Hematopathology, Advanced Centre for Treatment and Research in Cancer, Tata Memorial Centre, Mumbai, India

Homi Bhabha National Institute (HBNI), Mumbai, India

Search for more papers by this author
Shruti Ghai

Shruti Ghai

Department of Hematopathology, Advanced Centre for Treatment and Research in Cancer, Tata Memorial Centre, Mumbai, India

Search for more papers by this author
Nirmalya Roy Moulik

Nirmalya Roy Moulik

Homi Bhabha National Institute (HBNI), Mumbai, India

Pediatric Haematolymphoid Disease Management Group, Tata Memorial Centre, Mumbai, India

Search for more papers by this author
Dhanalaxmi Shetty

Dhanalaxmi Shetty

Homi Bhabha National Institute (HBNI), Mumbai, India

Department of Cancer Cytogenetics, Advanced Centre for treatment and research in cancer, Tata Memorial Centre, Mumbai, India

Search for more papers by this author
PG Subramanian

PG Subramanian

Department of Hematopathology, Advanced Centre for Treatment and Research in Cancer, Tata Memorial Centre, Mumbai, India

Homi Bhabha National Institute (HBNI), Mumbai, India

Search for more papers by this author
Prashant Tembhare

Prashant Tembhare

Department of Hematopathology, Advanced Centre for Treatment and Research in Cancer, Tata Memorial Centre, Mumbai, India

Homi Bhabha National Institute (HBNI), Mumbai, India

Search for more papers by this author
Sumeet Gujral

Sumeet Gujral

Department of Hematopathology, Advanced Centre for Treatment and Research in Cancer, Tata Memorial Centre, Mumbai, India

Homi Bhabha National Institute (HBNI), Mumbai, India

Search for more papers by this author
Chetan Dhamne

Chetan Dhamne

Homi Bhabha National Institute (HBNI), Mumbai, India

Pediatric Haematolymphoid Disease Management Group, Tata Memorial Centre, Mumbai, India

Search for more papers by this author
Sripad Banavali

Sripad Banavali

Homi Bhabha National Institute (HBNI), Mumbai, India

Pediatric Haematolymphoid Disease Management Group, Tata Memorial Centre, Mumbai, India

Search for more papers by this author
Gaurav Narula

Gaurav Narula

Homi Bhabha National Institute (HBNI), Mumbai, India

Pediatric Haematolymphoid Disease Management Group, Tata Memorial Centre, Mumbai, India

Search for more papers by this author
Nikhil Patkar

Corresponding Author

Nikhil Patkar

Department of Hematopathology, Advanced Centre for Treatment and Research in Cancer, Tata Memorial Centre, Mumbai, India

Homi Bhabha National Institute (HBNI), Mumbai, India

Correspondence

Nikhil Patkar, Department of Hematopathology, Advanced Centre for Treatment and Research in Cancer, Tata Memorial Centre, Navi Mumbai – 410210, Maharashtra, India.

Email: [email protected]

Search for more papers by this author
First published: 13 August 2021
Citations: 4

Shrinidhi Nathany and Gaurav Chatterjee have contributed equally to this work.

A part of this study was presented in the ASH 2019. The abstract has been published as “Gaurav Chatterjee, Gaurav Narula, Shrinidhi Nathany, Prashant Tembhare, Papagudi Ganesan Subramanian, Sumeet Gujral, Maya Prasad, Nirmalya Roy Moulik, Vasudev Bhat, Chetan A. Dhamne, Shripad Banavali, Nikhil Patkar; Genomic Landscape of Juvenile Myelomonocytic Leukemia: A Real World Context. Blood 2019; 134 (Supplement_1): 1728. doi: https://doi.org/10.1182/blood-2019-129750.”

Abstract

Introduction

Juvenile myelomonocytic leukemia (JMML) is a rare childhood neoplasm (<5% cases), which has been categorized under myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in the recent classification by the World Health Organization.

Methods

We developed a 51-gene (151.5kB) low-cost targeted myeloid panel based on single-molecule molecular inversion probes to comprehensively evaluate the genomic profile of Juvenile myelomonocytic leukemia (JMML).

Results

A total of 50 children with clinical and pathological features of JMML were sequenced at high coverage. Among the 50 patients, 44(88%) harbored mutations in one of the RAS/MAPK-pathway genes, most frequently in NRAS (32%), followed by PTPN11 (28%) and NF1 (22%). One-fifth of children had more than one mutation, with 5 cases harboring two RAS pathway mutations. Monosomy 7 was detected in 32% (16) patients, and five of these did not harbor any RAS pathway mutations. Children with monosomy 7 showed shorter overall survival compared with their wild-type counterparts (P = .02).

Conclusion

Our study highlights that comprehensive genomic profiling identifies at least one mutation in almost 90% of JMML patients. Performing genomic analysis at baseline might help in triaging children with JMML for allogenic stem cell transplant in resource-constrained settings.

CONFLICT OF INTEREST

The authors report no conflict of interest.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.