Therapy-related B-lymphoblastic leukemia associated with Philadelphia chromosome and MLL rearrangement: Single institution experience and the review of the literature

Pathol Int. 2015 Oct;65(10):536-40. doi: 10.1111/pin.12337. Epub 2015 Aug 11.

Abstract

Therapy related acute lymphoblastic leukemia (t-ALL) of B cell origin is rare and constitutes approximately 2% of all ALL. Previously compiled data on the complete cytogenetic analysis of 48 t-B-ALL cases suggested that MLL rearrangement at 11q23 gene locus is the most common abnormality. Philadelphia chromosome (Ph) and a normal karyotype were reported as the second and third most common karyotypes, respectively. We investigated cytogenetic karyotypes of six t-B-ALL cases with a pre-B cell immunophenotype. Ph + t-B-ALL was noted in four of six patients previously treated with radiation and/or chemotherapy. In addition, one case demonstrated MLL rearrangement at 11q23 locus while one case demonstrated normal cytogenetic karyotype. Five of the six t-B-ALL patients had persistent leukemia following initiation of chemotherapy for secondary leukemia with survival ranging from 10 to 21 months. To our knowledge, only fourteen patients with Ph + t-B-ALL have been described in the literature. In the current study, three of four cases with Ph + t-B-ALL were associated with treated breast carcinoma while one patient was treated for Hodgkin lymphoma. All four patients had undergone radiation therapy. The results may indicate a plausible association between Ph+t-B-ALL and prior radiation exposure.

Keywords: B-ALL; MLL; Philadelphia chromosome; therapy-related.

MeSH terms

  • Aged
  • Breast Neoplasms / genetics
  • Chromosomes, Human, Pair 11 / genetics
  • Cytogenetic Analysis / methods
  • Female
  • Gene Rearrangement / genetics*
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Immunophenotyping / methods
  • Karyotyping
  • Male
  • Middle Aged
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Neoplasms, Second Primary / diagnosis
  • Neoplasms, Second Primary / genetics
  • Neoplasms, Second Primary / pathology*
  • Philadelphia Chromosome*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Translocation, Genetic / genetics

Substances

  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase