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Genomic landscape of Juvenile Myelomonocytic Leukemia (JMML) - A real world context
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  • SHRINIDHI NATHANY,
  • Gaurav Chatterjee,
  • Shruti Ghai,
  • Nirmalya Roy Moulik,
  • Dhanlaxmi Shetty,
  • Papagudi Subramanian,
  • Prashant Tembhare,
  • Sumeet Gujral,
  • Chetan Dhamne,
  • Sripad Banavali,
  • Gaurav Narula,
  • Nikhil Patkar
SHRINIDHI NATHANY
Tata Memorial Centre
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Gaurav Chatterjee
Tata Memorial Centre
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Shruti Ghai
Tata Memorial Centre
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Nirmalya Roy Moulik
Tata Memorial Centre
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Dhanlaxmi Shetty
Tata Memorial Centre
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Papagudi Subramanian
Tata Memorial Centre
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Prashant Tembhare
Tata Memorial Centre
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Sumeet Gujral
Tata Memorial Hospital
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Chetan Dhamne
Tata Memorial Hospital
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Sripad Banavali
Tata Memorial Centre
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Gaurav Narula
Tata Memorial Centre
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Nikhil Patkar
Tata Memorial Centre
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Abstract

Background: JMML is a pediatric haematopoietic stem cell malignancy characterised by uncontrolled proliferation of myelomonocytic and progenitor compartments and a poor outcome. We comprehensively evaluated the genomic profile of JMML that presented to our hospital for diagnosis and treatment. Procedure: We developed a 51-gene (151.5kB) low-cost targeted myeloid panel based on single-molecule molecular inversion probes. A total of 50 children with clinical and pathological features of JMML were sequenced at high coverage on an Illumina MiSeq. The presenting clinical, laboratory and follow-up data were procured from the electronic medical record system of the institution. Results: The median age of our cohort was 2 years, with a male preponderance. Among the 50 patients, 43 (86%)harboured mutations in one of the RAS/MAPK-pathway genes, most frequently in PTPN11 (14, 28%), and NRAS (14, 28%), followed by NF1(11. 22%). Interestingly, 20% (10) of children had more than one mutation, with 5 cases harbouring two RAS-pathway mutations. Monosomy 7 was detected in 32% (16) patients, and five of these did not harbour any RAS-pathway mutations. The follow-up data revealed that 37 (74%) of these children had succumbed to the disease. Children with monosomy 7 showed shorter overall survival, compared to their wildtype counterparts (p=0.02). Conclusion: Our study highlights that comprehensive genomic profiling identifies at least one mutation in almost 90% of JMML patients. Performing genomic analysis early in evaluation of JMML might help in triaging patients for allogenic stem cell transplant in resource-constrained settings.