Analysis of loss of heterozygosity and X chromosome inactivation in spleens with myeloproliferative disorders and acute myeloid leukemia

Dennis P. O'Malley, Attilio Orazi, Mingsheng Wang, Liang Cheng

Research output: Contribution to journalArticle

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Abstract

Neoplastic myeloid proliferations are seen in the spleens of some patients with acute and chronic myeloproliferative disorders. Both acute myeloid leukemia (AML) and chronic myeloproliferative disorders have a variety of underlying cytogenetic defects that can be evaluated by loss of heterozygosity (LOH) studies. LOH studies have advantages over conventional cytogenetics by allowing the use of archival tissues. We evaluated the spleens in AML and chronic myeloproliferative disorders with neoplastic myeloid proliferations for the presence of LOH at several chromosome loci, and X-chromosome inactivation. A total of 17 spleens were evaluated (chronic myelogenous leukemia=6; chronic idiopathic myelofibrosis=6; essential thrombocythemia=1; AML arising from previous chronic myeloproliferative disorders=4). We examined LOH loci 7q (D7S2554), 8q (D8S263), 9p (D9S157, D9S161), 13q (D13S319), common sites of genetic abnormality in chronic myeloproliferative disorders, and TP53. In six cases, spleen LOH findings were compared to those of concurrent or preceding bone marrow biopsies. Five spleens of female patients were evaluated for the presence of clonality using X-chromosome inactivation. Of the 16 cases analyzed, 14 (88%) had at least one abnormal LOH locus, with 6/16 with two abnormal loci. The abnormalities were distributed as follows: D9S161-7/15 (47%), TP53-6/16 (38%), D7S2554-5/16 (31%), D9S157-5/15 (33%), D8S263-3/14 (21%), and D13S319-2/14 (14%). Of the six bone marrows, 4/6 showed concordance in bone marrow and spleen specimens, with additional LOH abnormalities being identified in the spleen specimens of all four cases. X-chromosome inactivation studies were showed nonrandom (clonal) patterns in two cases. Our results show that allelic losses were common in the neoplastic extramedullary hematopoiesis found in spleens of chronic myeloproliferative disorders and AML. Comparison of spleen and bone marrow specimens by LOH demonstrated additional abnormalities in the spleen compared to the marrow.

Original languageEnglish
Pages (from-to)1562-1568
Number of pages7
JournalModern Pathology
Volume18
Issue number12
DOIs
StatePublished - Dec 2005

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X Chromosome Inactivation
Myeloproliferative Disorders
Loss of Heterozygosity
Acute Myeloid Leukemia
Spleen
Bone Marrow
Cytogenetics
Extramedullary Hematopoiesis
Essential Thrombocythemia
Primary Myelofibrosis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chromosomes
Biopsy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Analysis of loss of heterozygosity and X chromosome inactivation in spleens with myeloproliferative disorders and acute myeloid leukemia. / O'Malley, Dennis P.; Orazi, Attilio; Wang, Mingsheng; Cheng, Liang.

In: Modern Pathology, Vol. 18, No. 12, 12.2005, p. 1562-1568.

Research output: Contribution to journalArticle

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abstract = "Neoplastic myeloid proliferations are seen in the spleens of some patients with acute and chronic myeloproliferative disorders. Both acute myeloid leukemia (AML) and chronic myeloproliferative disorders have a variety of underlying cytogenetic defects that can be evaluated by loss of heterozygosity (LOH) studies. LOH studies have advantages over conventional cytogenetics by allowing the use of archival tissues. We evaluated the spleens in AML and chronic myeloproliferative disorders with neoplastic myeloid proliferations for the presence of LOH at several chromosome loci, and X-chromosome inactivation. A total of 17 spleens were evaluated (chronic myelogenous leukemia=6; chronic idiopathic myelofibrosis=6; essential thrombocythemia=1; AML arising from previous chronic myeloproliferative disorders=4). We examined LOH loci 7q (D7S2554), 8q (D8S263), 9p (D9S157, D9S161), 13q (D13S319), common sites of genetic abnormality in chronic myeloproliferative disorders, and TP53. In six cases, spleen LOH findings were compared to those of concurrent or preceding bone marrow biopsies. Five spleens of female patients were evaluated for the presence of clonality using X-chromosome inactivation. Of the 16 cases analyzed, 14 (88{\%}) had at least one abnormal LOH locus, with 6/16 with two abnormal loci. The abnormalities were distributed as follows: D9S161-7/15 (47{\%}), TP53-6/16 (38{\%}), D7S2554-5/16 (31{\%}), D9S157-5/15 (33{\%}), D8S263-3/14 (21{\%}), and D13S319-2/14 (14{\%}). Of the six bone marrows, 4/6 showed concordance in bone marrow and spleen specimens, with additional LOH abnormalities being identified in the spleen specimens of all four cases. X-chromosome inactivation studies were showed nonrandom (clonal) patterns in two cases. Our results show that allelic losses were common in the neoplastic extramedullary hematopoiesis found in spleens of chronic myeloproliferative disorders and AML. Comparison of spleen and bone marrow specimens by LOH demonstrated additional abnormalities in the spleen compared to the marrow.",
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T1 - Analysis of loss of heterozygosity and X chromosome inactivation in spleens with myeloproliferative disorders and acute myeloid leukemia

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AU - Cheng, Liang

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