Characterization of unusual iAMP21 B-lymphoblastic leukemia (iAMP21-ALL) from the Mayo Clinic and Children's Oncology Group

Alaa Koleilat, James B. Smadbeck, Cinthya J. Zepeda-Mendoza, Cynthia M. Williamson, Beth A. Pitel, Crystal L. Golden, Xinjie Xu, Patricia T. Greipp, Rhett P. Ketterling, Nicole L. Hoppman, Jess F. Peterson, Christine J. Harrison, Yassmine M.N. Akkari, Karen D. Tsuchiya, Mary Shago, Linda B. Baughn

Research output: Contribution to journalArticlepeer-review


Acute lymphoblastic leukemia (B-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21-ALL) represents a recurrent high-risk cytogenetic abnormality and accurate identification is critical for appropriate clinical management. Identification of iAMP21-ALL has historically relied on fluorescence in situ hybridization (FISH) using a RUNX1 probe. Current classification requires ≥ five copies of RUNX1 per cell and ≥ three additional copies of RUNX1 on a single abnormal iAMP21-chromosome. We sought to evaluate the performance of the RUNX1 probe in the identification of iAMP21-ALL. This study was a retrospective evaluation of iAMP21-ALL in the Mayo Clinic and Children's Oncology Group cohorts. Of 207 cases of iAMP21-ALL, 188 (91%) were classified as “typical” iAMP21-ALL, while 19 (9%) cases were classified as “unusual” iAMP21-ALL. The “unusual” iAMP21 cases did not meet the current definition of iAMP21 by FISH but were confirmed to have iAMP21 by chromosomal microarray. Half of the “unusual” iAMP21-ALL cases had less than five RUNX1 signals, while the remainder had ≥ five RUNX1 signals with some located apart from the abnormal iAMP21-chromosome. Nine percent of iAMP21-ALL cases fail to meet the FISH definition of iAMP21-ALL demonstrating that laboratories are at risk of misidentification of iAMP21-ALL when relying only on the RUNX1 FISH probe. Incorporation of chromosomal microarray testing circumvents these risks.

Original languageEnglish (US)
Pages (from-to)710-719
Number of pages10
JournalGenes Chromosomes and Cancer
Issue number12
StatePublished - Dec 2022


  • B-ALL
  • FISH
  • RUNX1
  • cytogenetics
  • iAMP21-ALL

ASJC Scopus subject areas

  • Genetics
  • Cancer Research


Dive into the research topics of 'Characterization of unusual iAMP21 B-lymphoblastic leukemia (iAMP21-ALL) from the Mayo Clinic and Children's Oncology Group'. Together they form a unique fingerprint.

Cite this