Isolated del(5q) in myeloid malignancies: clinicopathologic and molecular features in 143 consecutive patients

Am J Hematol. 2011 May;86(5):393-8. doi: 10.1002/ajh.21984.

Abstract

World Health Organization (WHO) criteria were used to identify 143 consecutive patients (median age 73 years; 90 females) with myeloid neoplasms and isolated del(5q) seen between 1989 and 2009. We have previously reported on 88 (61%) of these patients who met criteria for WHO defined "myelodysplastic syndromes (MDS) with isolated del(5q)." The remaining 55 patients were classified as having "other" MDS variants (n = 29; 20%), acute myeloid leukemia (AML; n = 14; 10%), or myeloproliferative neoplasms (MPN; n = 12; 8%). DNA was available in 138 patients and mutation screening revealed 20 cases with JAK2, 6 with IDH, and 3 with MPL mutations; JAK2 and MPL mutations were seen mostly in MPN or "MDS with isolated del(5q)" whereas IDH mutations were frequent in other MDS variants. Overall median survival for the 143 patient cohort was 35 months and leukemic transformation (LT) was documented in 19 (~13%) cases. "MDS with isolated del(5q)" had the best prognosis with median survival of 66 months and LT rate of ~6%. Survival was poor among the other myeloid neoplasm subgroups regardless of specific morphologic diagnosis. Multivariable analysis identified higher leukocyte count and percentage of bone marrow and circulating blasts as independent predictors of shortened survival. The first two parameters and the presence of IDH mutations predicted inferior leukemia-free survival. The current study validates the prognostic relevance of considering "MDS with isolated del(5q)" as a separate WHO subcategory and identifies leukocytosis, higher blast count, and IDH mutations as being prognostically detrimental, in myeloid neoplasms associated with isolated del(5q).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Transformation, Neoplastic / genetics
  • Chromosome Deletion
  • Chromosomes, Human, Pair 15
  • Female
  • Follow-Up Studies
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Janus Kinase 2 / genetics
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / physiopathology*
  • Leukemia, Myeloid, Acute / therapy
  • Leukocytosis
  • Male
  • Medical Records
  • Middle Aged
  • Mutation
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / physiopathology*
  • Myelodysplastic Syndromes / therapy
  • Myeloproliferative Disorders / diagnosis
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / physiopathology*
  • Myeloproliferative Disorders / therapy
  • Prognosis
  • Receptors, Thrombopoietin / genetics
  • Retrospective Studies
  • Survival Analysis
  • United States

Substances

  • Receptors, Thrombopoietin
  • MPL protein, human
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • JAK2 protein, human
  • Janus Kinase 2

Supplementary concepts

  • Chromosome 15q, partial deletion