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Background <p>Acute promyelocytic leukemia (APL) is highly curable with targeted therapy combining all-trans retinoic acid (ATRA) and arsenic trioxide, yet the microgranular variant (M3v) frequently mimics monocytic leukemia and may delay diagnosis. Although FLT3 internal tandem duplications are common cooperating lesions, concurrent FLT3 tyrosine kinase domain (FLT3-TKD) mutations and MYC amplification remain rarely reported in APL.</p> Aim <p>We report a genomically defined case of M3v-APL harboring both FLT3-TKD (D835Y) and high-level MYC amplification (≥ 8 copies/cell).</p> Methods <p>A 35-year-old woman presenting with pancytopenia, disseminated intravascular coagulation, and prominent schistocytosis suggestive of secondary microangiopathic changes underwent immediate bone marrow examination, flow cytometry, FISH, RT-PCR, and targeted next-generation sequencing using a 54-gene myeloid panel.</p> Results <p>Diagnostic studies confirmed PML::RARA fusion (bcr-3 isoform), FLT3-TKD D835Y (variant allele frequency 42%), and high-level MYC amplification demonstrated by metaphase FISH analysis. Anthracycline-sparing induction with ATRA, arsenic trioxide, and a single dose of gemtuzumab ozogamicin (3&#xa0;mg/m²) achieved complete morphological remission by day 28.</p> Conclusions <p>This case expands the recognized genomic spectrum of microgranular APL and suggests a potentially relevant cooperative genomic pattern. Comprehensive genomic profiling at diagnosis may provide additional biological insights and could eventually support future risk-adapted therapeutic strategies. However, the clinical implications of this uncommon genomic constellation remain to be established in larger patient cohorts.</p>

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Microgranular acute promyelocytic leukemia with concurrent FLT3-TKD mutation and MYC amplification: expanding the genomic spectrum and guiding personalized therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月14日

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  • Yousef VatanParast

摘要

Background

Acute promyelocytic leukemia (APL) is highly curable with targeted therapy combining all-trans retinoic acid (ATRA) and arsenic trioxide, yet the microgranular variant (M3v) frequently mimics monocytic leukemia and may delay diagnosis. Although FLT3 internal tandem duplications are common cooperating lesions, concurrent FLT3 tyrosine kinase domain (FLT3-TKD) mutations and MYC amplification remain rarely reported in APL.

Aim

We report a genomically defined case of M3v-APL harboring both FLT3-TKD (D835Y) and high-level MYC amplification (≥ 8 copies/cell).

Methods

A 35-year-old woman presenting with pancytopenia, disseminated intravascular coagulation, and prominent schistocytosis suggestive of secondary microangiopathic changes underwent immediate bone marrow examination, flow cytometry, FISH, RT-PCR, and targeted next-generation sequencing using a 54-gene myeloid panel.

Results

Diagnostic studies confirmed PML::RARA fusion (bcr-3 isoform), FLT3-TKD D835Y (variant allele frequency 42%), and high-level MYC amplification demonstrated by metaphase FISH analysis. Anthracycline-sparing induction with ATRA, arsenic trioxide, and a single dose of gemtuzumab ozogamicin (3 mg/m²) achieved complete morphological remission by day 28.

Conclusions

This case expands the recognized genomic spectrum of microgranular APL and suggests a potentially relevant cooperative genomic pattern. Comprehensive genomic profiling at diagnosis may provide additional biological insights and could eventually support future risk-adapted therapeutic strategies. However, the clinical implications of this uncommon genomic constellation remain to be established in larger patient cohorts.