Distinct pathologic feature of myeloid neoplasm with t(v;11p15); NUP98 rearrangement

Hum Pathol. 2022 May:123:11-19. doi: 10.1016/j.humpath.2022.02.004. Epub 2022 Feb 12.


Chromosome rearrangements involving NUP98 at 11p15 are rare but recurring abnormalities in acute myeloid leukemia (AML). Here we described 12 cases of myeloid neoplasms with t(v; 11p15); NUP98 rearrangement and characterized their pathologic features. Our patient cohort included 10 adults and 2 children with a median age of 51 years. They were predominantly AML (n = 10) including de novo AML, therapy-related AML, chronic myeloid leukemia with myeloid blast crisis, and mixed phenotype acute leukemia, as well as therapy-related myelodysplastic syndrome (MDS) and MDS/myeloproliferative neoplasm with increased blasts. The blasts shared some common features including pink/red cytoplasmic granules, presence of a perinuclear hof, Auer rods, and occasional bilobed nuclei, mimicking acute promyelocytic leukemia (APML). Flow cytometric studies showed blasts positive for MPO, CD117, CD13 and CD33, with a subset of cases negative for CD34 and/or HLA-DR and a subset of cases expressing monocytic markers. The translocations of 11p15 included t(7; 11) (p15; p15), t(2; 11) (q31; p15), t(9; 11) (p22; p15), t(5; 11) (q32; p15), and t(11; 12) (p15; q13). Three cases showed cryptic NUP98 rearrangement. These patients showed incomplete response to therapy with median overall survival of 17.5 months, a complete remission rate of 25% following chemotherapy induction and primary refractory disease of 58%. It is clinically important to recognize this group of diseases because the blasts can be misclassified as promyelocytes, and NUP98 rearrangement may be cryptic requiring fluorescence in situ hybridization (FISH) study. This case series highlights that NUP98-rearranged myeloid neoplasms are clinically, morphologically, and cytogenetically distinct and could be considered as a separate entity in the WHO classification defined by cytogenetic abnormality.

Keywords: Morphology; Myeloid neoplasm; NUP98 FISH; NUP98 rearrangement; t(v;11p15).

MeSH terms

  • Chromosome Aberrations
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myeloid, Acute* / genetics
  • Middle Aged
  • Myeloproliferative Disorders* / genetics
  • Nuclear Pore Complex Proteins / genetics
  • Translocation, Genetic


  • Nuclear Pore Complex Proteins
  • Nup98 protein, human
  • nuclear pore complex protein 98