Intrachromosomal amplification of chromosome 21 (iAMP21) detected by ETV6/RUNX1 FISH screening in childhood acute lymphoblastic leukemia: a case report

Abstract

Chromosome abnormalities that usually define high-risk acute lymphoblastic leukemia are the t(9;22)/ breakpoint cluster region protein-Abelson murine leukemia viral oncogene homolog 1, hypodiploid with < 44 chromosomes and 11q23/ myeloid/lymphoid leukemia gene rearrangements. The spectrum of acute lymphoblastic leukemia genetic abnormalities is nevertheless rapidly expanding. Therefore, newly described chromosomal aberrations are likely to have an impact on clinical care in the near future. Recently, the rare intrachromosomal amplification of chromosome 21 started to be considered a high-risk chromosomal abnormality. It occurs in approximately 2-5% of pediatric patients with B-cell precursor acute lymphoblastic leukemia. This abnormality is associated with a poor outcome. Hence, an accurate detection of this abnormality is expected to become very important in the choice of appropriate therapy. In this work the clinical and molecular cytogenetic evaluation by fluorescence in situ hybridization of a child with B-cell precursor acute lymphoblastic leukemia presenting the rare intrachromosomal amplification of chromosome 21 is described.

Immunophenotypic challenges in diagnosis of CD79a negativity in a patient with B acute lymphoblastic leukemia harboring intrachromosomal amplification of chromosome 21: a case report

“…In a previous study, Harrison et al found that the median age of patients who have this abnormality is 9 years [18], which is close to the age of our patient (8 years), and the general data regarding the iAMP21 genetic abnormality are quite similar to our patient's data, with a lower WBC count (< 50.10 9 /L) [19], blasts presented in most cases with a common/pre B phenotype , dim or dim partial expression of CD45, and generally no expression of myeloid lineage markers [20]. Studies have recognized iAMP21 as one of the most important anomalies recently discovered in ALL, in which genotype has a direct impact on treatment [17]. Consequently, the World Health Organization (WHO) has included this genetic abnormality in their revised 2016 classification of malignancies of hematopoietic and lymphoid tissues under new provisional heading called leukemia/B lymphoblastic lymphoma with iAMP21 [10].…”

“…The obtained results reveal the existence of intrachromosomal amplification of chromosome 21 (iAMP21). iAMP21 is a rare genetic abnormality that occurs in about 2-5% of pediatric patients with B acute lymphoblastic leukemia [17]. It leads to an increase in the number of copies (amplification) of the RUNX1 gene, at least three more copies, on chromosome 21.…”

Molecular Profiling of Mammary Analog Secretory Carcinoma Revealed a Subset of Tumors Harboring a Novel ETV6-RET Translocation

“…The alternative ETV6-RET transcription will be important for treatment of those SCs with uncontrolled regional growth or SCs with metastatic foci, as treatment with entrectinib and similar drugs with the same target specificity will probably be ineffective in these SCs with alternative fusion transcript different from ETV6-NTRK3. The alternative fusion partner different from ETV6-NTRK3 in SC should not be of great surprise, because infantile fibrosarcoma with ETV6-NTRK3 translocation may have alternative EML4-NTRK3 translocation, 36 and there are descriptions of acute myeloid leukemias in which the ETV6 gene fuses with many alternative fusion partners, including ETV6-ABL1, 37 ETV6-LPXN, 38 ETV6-RUNX1, 39 ETV6-NCOA2, 40 and many others.…”

Implications of Intrachromosomal Amplification of Chromosome 21 on Outcome in Pediatric Acute Lymphoblastic Leukemia: Does It Affect Our Patients Too?

“…Intrachromosomal amplification of chromosome 21 (iAMP21) is a novel genetic entity of B-ALL that was identified as a distinct subgroup back in 2003. 11-13 It was identified by chance during the initial screening of patients with B-ALL using the same fluorescence in situ hybridization (FISH) probe used for detecting ETV6/RUNX1; t(12;21)(p13;q22), 3,6,11,14-17 and is caused by breakage-fusion-bridge cycles followed by chromothripsis resulting in the tandem amplifications on chromosome 21. 16,19,20…”