Topography, Clinical, and Genomic Correlates of 5q Myeloid Malignancies Revisited

Andres Jerez; Lukasz P. Gondek; Anna M. Jankowska; Hideki Makishima; Bartlomiej Przychodzen; Ramon V. Tiu; Christine L. O'Keefe; Azim M. Mohamedali; Denise Batista; Mikkael A. Sekeres; Michael A. McDevitt; Ghulam J. Mufti; Jaroslaw P. Maciejewski

doi:10.1200/JCO.2011.36.1824

Topography, Clinical, and Genomic Correlates of 5q Myeloid Malignancies Revisited

Andres Jerez, Lukasz P. Gondek, Anna M. Jankowska, Hideki Makishima, Bartlomiej Przychodzen, Ramon V. Tiu, Christine L. O'Keefe, Azim M. Mohamedali, Denise Batista, Mikkael A. Sekeres, Michael A. McDevitt, Ghulam J. Mufti, Jaroslaw P. Maciejewski^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

100 Citations (Scopus)

Abstract

Purpose

Interstitial deletions of chromosome 5q are common in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), pointing toward the pathogenic role of this region in disease phenotype and clonal evolution. The higher level of resolution of single-nucleotide polymorphism array (SNP-A) karyotyping may be used to find cryptic abnormalities and to precisely define the topographic features of the genomic lesions, allowing for more accurate clinical correlations.

Patients and Methods

We analyzed high-density SNP-A karyotyping at diagnosis for a cohort of 1,155 clinically well-annotated patients with malignant myeloid disorders.

Results

We identified chromosome 5q deletions in 142 (12%) of 1,155 patients and uniparental disomy segments (UPD) in four (0.35%) of 1,155 patients. Patients with deletions involving the centromeric and telomeric extremes of 5q have a more aggressive disease phenotype and additional chromosomal lesions. Lesions not involving the centromeric or telomeric extremes of 5q are not exclusive to 5q- syndrome but can be associated with other less aggressive forms of MDS. In addition, larger 5q deletions are associated with either del(17p) or UPD17p. In 31 of 33 patients with del(5q) AML, either a deletion involving the centromeric and/or telomeric regions or heterozygous mutations in NPM1 or MAML1 located in 5q35 were present.

Conclusion

Our results suggest that the extent of the affected region on 5q determines clinical characteristics that can be further modified by heterozygous mutations present in the telomeric extreme.

Original language	English
Pages (from-to)	1343-1349
Number of pages	7
Journal	Journal of Clinical Oncology
Volume	30
Issue number	12
DOIs	https://doi.org/10.1200/JCO.2011.36.1824
Publication status	Published - 20 Apr 2012

Keywords

COMMONLY DELETED REGION
MYELODYSPLASTIC SYNDROMES
CYTOGENETIC ABNORMALITIES
TP53 MUTATIONS
DEL(5Q)
LEUKEMIA
HETEROZYGOSITY
NUCLEOPHOSMIN
5Q-SYNDROME
DELINEATION

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1200/JCO.2011.36.1824

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Jerez, A., Gondek, L. P., Jankowska, A. M., Makishima, H., Przychodzen, B., Tiu, R. V., O'Keefe, C. L., Mohamedali, A. M., Batista, D., Sekeres, M. A., McDevitt, M. A., Mufti, G. J., & Maciejewski, J. P. (2012). Topography, Clinical, and Genomic Correlates of 5q Myeloid Malignancies Revisited. Journal of Clinical Oncology, 30(12), 1343-1349. https://doi.org/10.1200/JCO.2011.36.1824

@article{c631965da93b4943b970a67d56346ec7,

title = "Topography, Clinical, and Genomic Correlates of 5q Myeloid Malignancies Revisited",

abstract = "PurposeInterstitial deletions of chromosome 5q are common in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), pointing toward the pathogenic role of this region in disease phenotype and clonal evolution. The higher level of resolution of single-nucleotide polymorphism array (SNP-A) karyotyping may be used to find cryptic abnormalities and to precisely define the topographic features of the genomic lesions, allowing for more accurate clinical correlations.Patients and MethodsWe analyzed high-density SNP-A karyotyping at diagnosis for a cohort of 1,155 clinically well-annotated patients with malignant myeloid disorders.ResultsWe identified chromosome 5q deletions in 142 (12%) of 1,155 patients and uniparental disomy segments (UPD) in four (0.35%) of 1,155 patients. Patients with deletions involving the centromeric and telomeric extremes of 5q have a more aggressive disease phenotype and additional chromosomal lesions. Lesions not involving the centromeric or telomeric extremes of 5q are not exclusive to 5q- syndrome but can be associated with other less aggressive forms of MDS. In addition, larger 5q deletions are associated with either del(17p) or UPD17p. In 31 of 33 patients with del(5q) AML, either a deletion involving the centromeric and/or telomeric regions or heterozygous mutations in NPM1 or MAML1 located in 5q35 were present.ConclusionOur results suggest that the extent of the affected region on 5q determines clinical characteristics that can be further modified by heterozygous mutations present in the telomeric extreme.",

keywords = "COMMONLY DELETED REGION, MYELODYSPLASTIC SYNDROMES, CYTOGENETIC ABNORMALITIES, TP53 MUTATIONS, DEL(5Q), LEUKEMIA, HETEROZYGOSITY, NUCLEOPHOSMIN, 5Q-SYNDROME, DELINEATION",

author = "Andres Jerez and Gondek, {Lukasz P.} and Jankowska, {Anna M.} and Hideki Makishima and Bartlomiej Przychodzen and Tiu, {Ramon V.} and O'Keefe, {Christine L.} and Mohamedali, {Azim M.} and Denise Batista and Sekeres, {Mikkael A.} and McDevitt, {Michael A.} and Mufti, {Ghulam J.} and Maciejewski, {Jaroslaw P.}",

year = "2012",

month = apr,

day = "20",

doi = "10.1200/JCO.2011.36.1824",

language = "English",

volume = "30",

pages = "1343--1349",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "12",

}

TY - JOUR

T1 - Topography, Clinical, and Genomic Correlates of 5q Myeloid Malignancies Revisited

AU - Jerez, Andres

AU - Gondek, Lukasz P.

AU - Jankowska, Anna M.

AU - Makishima, Hideki

AU - Przychodzen, Bartlomiej

AU - Tiu, Ramon V.

AU - O'Keefe, Christine L.

AU - Mohamedali, Azim M.

AU - Batista, Denise

AU - Sekeres, Mikkael A.

AU - McDevitt, Michael A.

AU - Mufti, Ghulam J.

AU - Maciejewski, Jaroslaw P.

PY - 2012/4/20

Y1 - 2012/4/20

N2 - PurposeInterstitial deletions of chromosome 5q are common in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), pointing toward the pathogenic role of this region in disease phenotype and clonal evolution. The higher level of resolution of single-nucleotide polymorphism array (SNP-A) karyotyping may be used to find cryptic abnormalities and to precisely define the topographic features of the genomic lesions, allowing for more accurate clinical correlations.Patients and MethodsWe analyzed high-density SNP-A karyotyping at diagnosis for a cohort of 1,155 clinically well-annotated patients with malignant myeloid disorders.ResultsWe identified chromosome 5q deletions in 142 (12%) of 1,155 patients and uniparental disomy segments (UPD) in four (0.35%) of 1,155 patients. Patients with deletions involving the centromeric and telomeric extremes of 5q have a more aggressive disease phenotype and additional chromosomal lesions. Lesions not involving the centromeric or telomeric extremes of 5q are not exclusive to 5q- syndrome but can be associated with other less aggressive forms of MDS. In addition, larger 5q deletions are associated with either del(17p) or UPD17p. In 31 of 33 patients with del(5q) AML, either a deletion involving the centromeric and/or telomeric regions or heterozygous mutations in NPM1 or MAML1 located in 5q35 were present.ConclusionOur results suggest that the extent of the affected region on 5q determines clinical characteristics that can be further modified by heterozygous mutations present in the telomeric extreme.

AB - PurposeInterstitial deletions of chromosome 5q are common in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), pointing toward the pathogenic role of this region in disease phenotype and clonal evolution. The higher level of resolution of single-nucleotide polymorphism array (SNP-A) karyotyping may be used to find cryptic abnormalities and to precisely define the topographic features of the genomic lesions, allowing for more accurate clinical correlations.Patients and MethodsWe analyzed high-density SNP-A karyotyping at diagnosis for a cohort of 1,155 clinically well-annotated patients with malignant myeloid disorders.ResultsWe identified chromosome 5q deletions in 142 (12%) of 1,155 patients and uniparental disomy segments (UPD) in four (0.35%) of 1,155 patients. Patients with deletions involving the centromeric and telomeric extremes of 5q have a more aggressive disease phenotype and additional chromosomal lesions. Lesions not involving the centromeric or telomeric extremes of 5q are not exclusive to 5q- syndrome but can be associated with other less aggressive forms of MDS. In addition, larger 5q deletions are associated with either del(17p) or UPD17p. In 31 of 33 patients with del(5q) AML, either a deletion involving the centromeric and/or telomeric regions or heterozygous mutations in NPM1 or MAML1 located in 5q35 were present.ConclusionOur results suggest that the extent of the affected region on 5q determines clinical characteristics that can be further modified by heterozygous mutations present in the telomeric extreme.

KW - COMMONLY DELETED REGION

KW - MYELODYSPLASTIC SYNDROMES

KW - CYTOGENETIC ABNORMALITIES

KW - TP53 MUTATIONS

KW - DEL(5Q)

KW - LEUKEMIA

KW - HETEROZYGOSITY

KW - NUCLEOPHOSMIN

KW - 5Q-SYNDROME

KW - DELINEATION

U2 - 10.1200/JCO.2011.36.1824

DO - 10.1200/JCO.2011.36.1824

M3 - Article

SN - 0732-183X

VL - 30

SP - 1343

EP - 1349

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 12

ER -

Topography, Clinical, and Genomic Correlates of 5q Myeloid Malignancies Revisited

Abstract

Keywords

UN SDGs

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