HAEM5:Myelodysplastic neoplasm with low blasts and 5q deletion

Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Myelodysplastic Syndrome (MDS) with Isolated del(5q).

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Primary Author(s)*

Xiaolin Hu, Ph.D; Teresa Smolarek, Ph.D, FACMG

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
Category	Myeloid proliferations and neoplasms
Family	Myelodysplastic neoplasms
Type	Myelodysplastic neoplasms, with defining genetic abnormalities
Subtype(s)	Myelodysplastic neoplasm with low blasts and 5q deletion

Definition / Description of Disease

MDS with isolated del(5q) is a type of MDS with defining cytogenetic abnormality of del(5q). The World Health Organization named it as isolated del 5q, but occasionally the deletion can occur with an additional cytogenetic abnormality other than monosomy 7 or del(7q). The 5q- syndrome was first described by Van den Berghe et al as a distinct type of MDS featured with macrocytic anemia, hypolobulated megakaryocytes, a normal or increased platelet count . Deletion of 5q is the most common recurrent cytogenetic abnormality in myeloid neoplasm and it was commonly seen in 10-15% of patients with MDS. A ~1.5 Mb common deleted region (CDR) at 5q32-q33 was identified in 5q- syndrome patients and was associated with good prognosis . This disease has a good respond to lenalidomide treatment (See Clinical Significance).

Synonyms / Terminology

Myelodysplastic syndromes with 5q deletion; 5q minus syndrome

Epidemiology / Prevalence

• Median age 67 years
• Women versus male about 2:1

Clinical Features

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Signs and Symptoms	EXAMPLE: Asymptomatic (incidental finding on complete blood counts) EXAMPLE: B-symptoms (weight loss, fever, night sweats) EXAMPLE: Fatigue EXAMPLE: Lymphadenopathy (uncommon)
Laboratory Findings	EXAMPLE: Cytopenias EXAMPLE: Lymphocytosis (low level)

editv4:Clinical Features

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• Macrocytic anemia most common, usually severe and can be transfusion dependent.
• Thrombocytosis can be seen in 1/3 to 1/2 of cases, whereas thrombocytopenia or neutropenia are uncommon.
• Pancytopenia is rare. If pancytopenia with isolated 5q-, MDS with unclassifiable should be considered. [WHO]
• Good prognosis and low risk to progress to AML.

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Sites of Involvement

Blood or bone marrow

Morphologic Features

On bone marrow examination, cellularity is usually normal or hypercellular. Erythroid hypoplasia may be seen. Blasts cells are < 5% in the bone marrow and < 1% in the peripheral blood. The most characteristic feature of isolated 5q- is the presence of micromegakaryocytes with hypolobated nuclei [insert pic micromegakaryocyte]. The erythroid dysplasia may be seen but not predominant. Granulocytic dysplasia is uncommon.

Hypolobated micromegakaryocytes are also seen in CML, which is characterized by leukocytosis, basophilia, and myeloid hyperplasia with leftward shift. Platelet count increase can be seen in essential thrombocythemia (ET), but ET has large megakaryocytes with hyperlobulated nuclei rather than microkaryocytes with hypolobulation in MDS with isolated del(5q).

Immunophenotype

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Finding	Marker
Positive (universal)	EXAMPLE: CD1
Positive (subset)	EXAMPLE: CD2
Negative (universal)	EXAMPLE: CD3
Negative (subset)	EXAMPLE: CD4

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There is no distinct immunophenotypic profile specific for myelodysplastic syndrome (MDS) with isolated del(5q). Currently, morphologic evaluation remains the gold standard in diagnosis of MDS. Immunophenotyping provides supportive evidence to clarify the blasts nature and percentage .

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Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: t(9;22)(q34;q11.2)	EXAMPLE: 3'ABL1 / 5'BCR	EXAMPLE: der(22)	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add reference)	Yes	No	Yes	EXAMPLE: The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).

editv4:Chromosomal Rearrangements (Gene Fusions)

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NA

Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence
EXAMPLE: t(9;22)(q34;q11.2)	EXAMPLE: 3'ABL1 / 5'BCR	EXAMPLE: der(22)	EXAMPLE: 5%
EXAMPLE: t(8;21)(q22;q22)	EXAMPLE: 5'RUNX1 / 3'RUNXT1	EXAMPLE: der(8)	EXAMPLE: 5%

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editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).

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• Chromosomal Rearrangements (Gene Fusions)
• Individual Region Genomic Gain/Loss/LOH
• Characteristic Chromosomal Patterns
• Gene Mutations (SNV/INDEL)

Diagnosis:

• Cytopenia in 1 to 2 lineages. Cytopenias are defined as hemoglobin concentration < 10 g/dL, platelet count < 100 x 10⁹/L and absolute neutrophil count < 1.8 x 10⁹/L; mild degree of anemia (hemoglobin < 13 g/dL in men or < 12 g/dL in women) or thrombocytopenia (platelets < 150 x10⁹/L) are allowed if defining cytogenetic abnormality is present. Thrombocytosis (platelet count ≥ 450 x 10⁹/L) is allowed in MDS with isolated del(5q). PB monocytes must be < 1 x10⁹/L.
• Dysplasia in 1 to 3 lineages. Micromegakaryocytes with hypolobation are characteristic dysplasia. Ring sideroblasts are not common.
• Blasts percentage: BM <5%, PB <1%, no Auer rods.
• Interstitial deletion of 5q alone or with an additional abnormality other than loss of chromosome 7 or deletion of 7q.
• Chromosome 7 loss or del(7q), more than one additional cytogenetic abnormality, excess blasts need to be excluded from the diagnosis.

Prognosis:

• According to IPSS‐R good‐risk group with low rates of leukemic transformation .
• The median survival of MDS with isolated del(5q) is 66 to 145 months.
• About less than 10% of cases progress to acute myeloid leukemia .
• Mutations of TP53 may function as an independent prognostic factor in associated with leukemic progression and resistant to lenalidomide.

Therapeutic Implications:

Lenalidomide is an analogue of thalidomide which functions as an immunomodulatory agent. Treatment with lenalidomide has shown great potential in reducing the abnormal clone as well as transfusion dependency irrespective of cytogenetic complexity . FDA approved Lenalidomide on December 2005 for treating MDS with del(5q) with or without additional cytogenetic abnormalities.

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Individual Region Genomic Gain / Loss / LOH

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Chr #	Gain / Loss / Amp / LOH	Minimal Region Genomic Coordinates [Genome Build]	Minimal Region Cytoband	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: 7	EXAMPLE: Loss	EXAMPLE: chr7:1- 159,335,973 [hg38]	EXAMPLE: chr7	Yes	Yes	No	EXAMPLE: Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
EXAMPLE: 8	EXAMPLE: Gain	EXAMPLE: chr8:1-145,138,636 [hg38]	EXAMPLE: chr8	No	No	No	EXAMPLE: Common recurrent secondary finding for t(8;21) (add reference).

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Chromosome Number	Gain/Loss/Amp/LOH	Region
EXAMPLE: 8	EXAMPLE: Gain	EXAMPLE: chr8:0-1000000
EXAMPLE: 7	EXAMPLE: Loss	EXAMPLE: chr7:0-1000000

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Characteristic Chromosomal Patterns

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Chromosomal Pattern	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: Co-deletion of 1p and 18q	Yes	No	No	EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

editv4:Characteristic Chromosomal Aberrations / Patterns

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The most characteristic cytogenetic abnormality is an interstitial deletion on the long arm of chromosome 5 or del(5q) The break point is not fixed but the region between bands q31 and q33 is generally deleted. Several candidates genes were thought to contribute to the haploinsufficiency effect of the deleted region, including RPS14 , CSNK1A1 , miR-145 and miR-146a . Identification of del(5q) has clinical significance because patients with this cytogenetic abnormality have a good prognosis and they respond well to lenalidomide treatment.

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Gene Mutations (SNV / INDEL)

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Gene; Genetic Alteration	Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)	Prevalence (COSMIC / TCGA / Other)	Concomitant Mutations	Mutually Exclusive Mutations	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: TP53; Variable LOF mutations EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations	EXAMPLE: TSG	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add Reference)	EXAMPLE: IDH1 R123H	EXAMPLE: EGFR amplification				EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

editv4:Gene Mutations (SNV/INDEL)

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Somatic mutations in JAK2 and MPL have been reported in a small subset patients with isolated del(5q), but these mutations seem not confer diagnostic or prognostic value . A subset of cases could have SF3B1 mutations, which needs to be differentiated with MDS-RS.

Gene	Mutation	Oncogene/Tumor Suppressor/Other	Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)	Prevalence (COSMIC/TCGA/Other)
EXAMPLE: TP53	EXAMPLE: R273H	EXAMPLE: Tumor Suppressor	EXAMPLE: LOF	EXAMPLE: 20%

Other Mutations

Type	Gene/Region/Other
Concomitant Mutations	JAK2 V617F, MPL W515L
Secondary Mutations
Mutually Exclusive

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Epigenomic Alterations

Genes involved in epigenetic regulation are frequently mutated in MDS such as TET2, DNMT3A, IDH1, IDH2, AXSL1, and EZH2 . These genes play a role in DNA methylation and chromatin modification as well as regulating gene expression.

Genes and Main Pathways Involved

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Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations	EXAMPLE: MAPK signaling	EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations	EXAMPLE: Cell cycle regulation	EXAMPLE: Unregulated cell division
EXAMPLE:  KMT2C and ARID1A; Inactivating mutations	EXAMPLE:  Histone modification, chromatin remodeling	EXAMPLE:  Abnormal gene expression program

editv4:Genes and Main Pathways Involved

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Several candidate genes in the common deleted region of 5q have been reported to contribute to the molecular pathogenesis.

RPS14: Encodes for ribosomal subunit of 40S. Inactivation of RPS14 results in ineffective erythroid differentiation and increased apoptosis in a p53 dependent way .

CSNK1A1: Encodes for CK1α, a serine/threonine protein kinase activity. Mutations in CSNK1A1 lead to clonal expansion of hematopoietic stem cells through activation of β-catenin .

miR-145 and miR146α: These two micro RNA genes are thought to be associated with thrombocytosis and hypolobulated megakaryocytes .

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Genetic Diagnostic Testing Methods

• Bone marrow morphology and peripheral blood test are standard in diagnosis of MDS.
• FISH probes targeting the CDR are commonly incorporated into MDS panel to assess -5/5q-.
• Conventional cytogenetics are also helpful in diagnosis.

  

  Fluorescent in situ hybridization (FISH) with a dual color DNA probe specific for the EGR1 (5q31.2) locus and to a distal short arm locus (5p15.31) of chromosome 5 detected two green and one red signal pattern that consistents with 5q deletion in 51% of patient's cells.

Familial Forms

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Additional Information

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Links

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References

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Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome. *Citation of this Page: “Myelodysplastic neoplasm with low blasts and 5q deletion”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 02/10/2025, https://ccga.io/index.php/HAEM5:Myelodysplastic_neoplasm_with_low_blasts_and_5q_deletion.