Ann Lab Med.  2025 Mar;45(2):133-145. 10.3343/alm.2024.0477.

Abnormalities in Chromosomes 5 and 7 in Myelodysplastic Syndrome and Acute Myeloid Leukemia

• Kendrick TS
• Buic D
• Fuller KA
• Erber WN

• KMID: 2565645
• DOI: http://doi.org/10.3343/alm.2024.0477

Abstract

Chromosomes 5 and 7 are large chromosomes that contain close to 1,000 genes each. Deletions of the long arms or loss of the entire chromosome (monosomy) are common defects in myeloid disorders, particularly MDS and AML. Loss of material from either chromosome 5 or 7 results in haploinsufficiency of multiple genes, with some implicated in leukemogenesis. Abnormalities of one or both occur in up to 15% of MDS and AML cases and co-segregate in half of these. Generally, these chromosomal abnormalities are harbingers of adverse risk in both myeloid disorders. A notable exception is del(5q) in 5q– syndrome, a subtype of MDS. In this review, we describe the pathogenesis and genetic consequences of deletions in chromosomes 5 and 7. Furthermore, we provide an overview of current testing methodologies used in the assessment of these chromosomal defects in hematological malignancies and describe the disease associations and prognostic implications of aberrations in chromosomes 5 and 7 in both MDS and AML.

Keyword

Acute myeloid leukemia; Chromosome 5; Chromosome 7; Monosomy; Myelodysplastic syndrome

Figure

• 

  Fig. 1 CDRs and CCRs of chromosome 5q associated with MDS and AML. The distal CDR (CDR-1) is located at 5q33 and is associated with the deletion of RPS14 and 5q– syndrome. The proximal CDR (CDR-2) at 5q31 encompasses genes, including EGR1, CSNK1A1, and G3BP1, and is associated with aggressive MDS and AML. CRRs are shown in green. This figure was created with BioRender.com. Abbreviations: MDS, myelodysplastic syndrome; CDR, commonly deleted region; CRR, commonly retained region; RPS14, ribosomal protein S14; EGR1, early growth response 1; CSNK1A1, casein kinase 1 alpha 1; G3BP1, G3BP stress granule assembly factor 1; NPM1, nucleophosmin 1; DDX41, DEAD-box helicase 41.

• 

  Fig. 2 CDRs of chromosome 7q associated with MDS and AML. The CDR on chromosome 7q spans 7q21.13–7q36.3, with regions corresponding to bands 7q31.33, 7q34, and 7q35–7q36.1 deleted in the majority of cases [15]. Genes of interest in the pathogenesis of –7/del(7q) myeloid neoplasms include SAMD9/SAMD9L, CUX1, and EZH2. This figure was created with BioRender.com. Abbreviations: MDS, myelodysplastic syndrome; CDR, commonly deleted region; SAMD9/SAMD9L, sterile alpha motif domain-containing 9/sterile alpha motif domain-containing 9-like; CUX1, cut-like homeobox 1; EZH2, enhancer of zeste 2 polycomb-repressive complex 2 subunit.

• 

  Fig. 3 Examples of chromosome abnormalities via karyotyping and FISH. (A) Karyotype of AML with a monosomal karyotype, with losses of multiple chromosomes, including monosomy 7. (B) del(5q) in a case of AML. FISH using a dual color probe set for EGR1 (5q31) and D5S23 (5p15.2) (one orange signal for EGR1 and two green signals for D5S23). Abbreviations: EGR1, early growth response 1; D5S23, human D5S23 control region on 5p.

• 

  Fig. 4 Bone marrow morphology of a myelodysplastic neoplasm with low blasts and isolated del(5q). (A) Bone marrow aspirate showing a small megakaryocyte with a non-lobated eccentric nucleus (Romanowsky staining, 1,000×). (B) Section of the bone marrow trephine showing megakaryocytic hyperplasia with a predominance of characteristic small forms with hypolobated nuclei (hematoxylin and eosin staining, 400×).

Reference

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