Guillermo Garcia-Manero MD

University of Texas MD Anderson Cancer Center, Houston, TX, United States

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Publications (2)10.4 Total impact

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    ABSTRACT: BACKGROUND:Isolated isochromosome (17q) is a rare cytogenetic abnormality in Philadelphia chromosome-negative myeloid neoplasms, usually myelodysplastic and/or myeloproliferative neoplasms (MDS/MPN). De novo acute myeloid leukemia (AML) with isochromosome 17q has rarely been reported. The frequency of genetic mutations is unknown.METHODS:The authors assessed clinicopathologic, immunophenotypic, and molecular genetic features of 22 myeloid neoplasms with isolated isochromosome 17q.RESULTS:Fourteen patients presented as MDS/MPN; 8 as de novo AML. Most presented with leukocytosis, anemia, thrombocytopenia, and splenomegaly. Morphologically, all showed myelodysplastic and myeloproliferative features, including pseudo-Pelger-Huet-like neutrophils, micromegakaryocytic hyperplasia, hypercellularity, fibrosis, and osteosclerosis. Blasts were increased (median, 40% in de novo AML; 9% in MDS/MPN). Immunohistochemical assessment of proliferation and apoptosis rates in AML were similar to a matched group without isochromosome 17q. In most patients, isochromosome 17q occurred at time of blast transformation or disease progression. DNA sequencing revealed no mutation in the uninvolved TP53 allele. Mutational analyses showed rare mutations in NRAS (3 of 10), FLT3 (2 of 16), and JAK2 (1 of 18), and no mutations in NPM1 (0 of 15), KIT (0 of 4), and CEBPA (0 of 4). The median overall survival was 14.5 months for de novo AML, and 11.0 months for MDS/MPN. With a median follow-up of 8.5 months (range, 1.5-107 months), 15 died of disease, 6 had persistent disease, and 1 was in remission after bone marrow transplantation.CONCLUSIONS:The authors conclude that myeloid neoplasms with isolated isochromosome 17q represent a distinct clinicopathologic entity with myelodysplastic and myeloproliferative features, high risk of leukemic transformation, and wild-type TP53. Cancer 2011;. © 2011 American Cancer Society.
    Cancer 10/2011; 118(11):2879 - 2888. · 5.20 Impact Factor
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    ABSTRACT: BACKGROUND:Nucleophosmin (NPM1) gene mutations are reported to predict a favorable prognosis in acute myeloid leukemia (AML) patients. Aberrant cytoplasmic localization of nucleophosmin (NPM) protein is reported be a surrogate for NPM1 gene mutation.METHODS:Using immunohistochemical (IHC) analysis, we assessed for NPM (clone 376) expression in formalin-fixed, formic acid-decalcified bone marrow biopsy specimens. DNA sequencing of exon 12 of NPM1 gene was performed in 104 patients.RESULTS:The study included 252 AML patients: 192 de novo AML, 33 AML preceded by either myelodysplastic syndrome or chronic myelomonocytic leukemia, and 27 therapy-related AML. The median age was 62 years and 115 patients were ≤60 years old. All patients received intensive chemotherapy. Cytoplasmic NPM was detected in 59 of 252 (23%) patients, including 48 of 192 (25%) de novo AML and 33 of 94 (35%) with a normal karyotype. DNA sequencing identified NPM1 mutations in 30 of 38 cases with cytoplasmic NPM and 10 of 66 cases with nuclear NPM. Cytoplasmic NPM was associated with young patient age (P = .024), FLT3/ITD (P = .005), CD34 negative blasts (P < .001), high peripheral blood blast count (P = .041), and high serum albumin level (P = .028). No statistical differences in overall or event-free survival were found on the basis of NPM localization. Similar results were obtained in patients ≤60 years old with normal karyotype and wild-type FLT3 (P = .768).CONCLUSIONS:IHC assessment for NPM localization did not predict prognosis in this patient cohort. The discordance between immunohistochemistry and DNA sequencing results indicates that DNA sequencing cannot be replaced by IHC assessment. Cancer 2009. © 2009 American Cancer Society.
    Cancer 10/2009; 115(20):4737 - 4744. · 5.20 Impact Factor