Institution: University of Texas MD Anderson Cancer Center
Additional authors:Rashmi Kanagal-Shamanna, Carlos E. Bueso-Ramos, L. Jeffrey Medeiros, C. Cameron Yin
Session: Therapy-related myeloid neoplasms
HISTORY
The patient was a 25-year-old woman who was diagnosed with T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) in September 2003. She received hyper-CVAD and methotrexate, and went into complete remission. In May 2004, the patient was found to have anemia and a bone marrow (BM) biopsy showed acute leukemia suggestive of myeloid immunophenotype. She was transferred to our hospital for further treatment options.
Upon presentation at our hospital, a complete blood cell count showed white blood cell 1.5 K/uL, hemoglobin 10.5 g/dL, and platelet count 32 K/uL. Her serum lactate dehydrogenase (466 IU/L) and b2-microglobulin (1.6 mg/L) level were within normal limits. A BM biopsy confirmed acute myeloid leukemia with maturation with 23% blasts. She was treated with fludarabine and cytarabine, but did not go into a remission. She was then given cyclophosphamide, cytarabine, and topotecan. However, she was still unable to achieve a remission. The patient died 2 months after relapse.DETAILS
The BM biopsy showed a hypercellular bone morrow with dysplastic megakaryocyte hyperplasia, and increased immature cells. The aspirate smear showed trilineage dysplasia and 23% blasts. The blasts were intermediate to large with fine chromatin, prominent nucleoli, and scant to moderate amount of cytoplasm.
IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Flow cytometry immunophenotypic analysis of the BM aspirate material revealed a distinct population of blasts that were positive for CD7, CD13, CD33, CD34, CD38, CD52, CD117, HLA-DR and myeloperoxidase, and were negative for CD2, CD3, CD5, CD9, CD10, CD14, CD19, CD20, CD41, CD56, CD64 and TdT, consistent with myeloid immunophenotype.
CYTOGENETIC FINDINGS
Conventional cytogenetic analysis of the BM aspirate specimen collected in May 2004 showed 46,XX,i(17)(q10)[12]/46,XX[8].
MOLECULAR FINDINGS
A missense mutation in exon 7 of the MDM4 gene (I175T) was detected by Sanger sequencing. Sanger sequencing of the entire coding region of TP53 including 5’ and 3’ UTR revealed a polymorphism variant P72R. No mutation was detected in TP53 gene, MDM2 gene or exon 12 of NPM1 gene.
INTERESTING FEATURES
Isolated isochromosome (17q) is a rare cytogenetic abnormality in Philadelphia chromosome-negative myeloid neoplasms, usually myelodysplastic and/or myeloproliferative. De novo AML with i(17q) has rarely been reported. We present a case of AML with isolated i(17q) in a patient with a history of T-ALL. Morphologically, the case showed both myelodysplastic and myeloproliferative features, including pseudo-Pelger-Huet-like neutrophils, micromegakaryotes hyperplasia, and hypercellularity. Sequencing analysis showed wild type TP53, but a mutation in MDM4 was detected, which may play a role in the leukemic transformation of this case with i(17q).
PROPOSED DIAGNOSIS
Acute myeloid leukemia with isolated i(17q) and MDM4 mutation
CONSENSUS DIAGNOSIS
Therapy-related myeloid neoplasm, acute myeloid leukemia with i(17q) and MDM4 mutation