Acute Myeloid Leukemia With t(6;9)(p23;q34) Is Associated With Dysplasia and a High Frequency of flt3 Gene Mutations

Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
American Journal of Clinical Pathology (Impact Factor: 2.51). 10/2004; 122(3):348-58. DOI: 10.1309/5DGB-59KQ-A527-PD47
Source: PubMed


We report 12 cases of t(6;9)(p23;q34)-positive acute myeloid leukemia (AML), all classified using the criteria of the World Health Organization classification. There were 10 women and 2 men with a median age of 51 years (range, 20-76 years). Dysplasia was present in all cases (9 previously untreated), and basophilia was present in 6 (50%). Immunophenotypic studies showed that the blasts were positive for CD9, CD13, CD33, CD38, CD117, and HLA-DR in all cases assessed. CD34 was positive in 11 (92%) of 12, and terminal deoxynucleotidyl transferase was positive in 7 (64%) of 11 cases. The t(6;9) was the only cytogenetic abnormality detected in 7 cases (58%), and 5 cases had additional chromosomal abnormalities. Of 8 cases assessed, 7 (88%) had flt3 gene mutations. We conclude that t(6;9)-positive AML cases have distinctive morphologic features, an immunophenotype suggesting origin from an early hematopoietic progenitor cell, and a high frequency of flt3 gene mutations.

Download full-text


Available from: L. Jeffrey Medeiros,
1 Follower
213 Reads
  • Source
    • "Among acute promyelocytic leukemia patients with PML-RARα, it was reported that 30-50% of patients had FLT3 mutations [55-57]. In addition, frequent (88~90%) co-occurrence was reported in patients with t(6; 9) and FLT3-ITD [55,58]. Similarly, FLT3-ITD was frequently found in patients with MLL-PTD [59]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The development of acute myeloid leukemia (AML) is a multistep process that requires at least two genetic abnormalities for the development of the disease. The identification of genetic mutations in AML has greatly advanced our understanding of leukemogenesis. Recently, the use of novel technologies, such as massively parallel DNA sequencing or high-resolution single-nucleotide polymorphism arrays, has allowed the identification of several novel recurrent gene mutations in AML. The aim of this review is to summarize the current findings for the identification of these gene mutations (Dnmt, TET2, IDH1/2, NPM1, ASXL1, etc.), most of which are frequently found in cytogenetically normal AML. The cooperative interactions of these molecular aberrations and their interactions with class I/II mutations are presented. The prognostic and predictive significances of these aberrations are also reviewed.
    Journal of Hematology & Oncology 09/2011; 4(1):36. DOI:10.1186/1756-8722-4-36 · 4.81 Impact Factor
  • Source
    • "Among APL patients with PML-RARα, it was reported that 30-50% of the patients had FLT3 mutations [4,27,33]. Frequent (~90%) co-occurrence was reported in patients with t(6; 9) and FLT3-ITD mutations [27,34]. Similarly, FLT3-ITD mutations are also frequently found in patients with mixed lineage leukemia (MLL)-partial tandem duplication (PTD) [35]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: FLT3 is a type III receptor tyrosine kinase. Mutations of FLT3 comprise one of the most frequently identified types of genetic alterations in acute myeloid leukemia. One-third of acute myeloid leukemia patients have mutations of this gene, and the majority of these mutations involve an internal tandem duplication in the juxtamembrane region of FLT3, leading to constitutive activation of downstream signaling pathways and aberrant cell growth. This review summarizes the current understanding of the effects of the downstream molecular signaling pathways after FLT3 activation, with a particular focus on the effects on transcription factors. Moreover, this review describes novel FLT3-targeted therapies, as well as efficient combination therapies for FLT3-mutated leukemia cells.
    Journal of Hematology & Oncology 04/2011; 4(1):13. DOI:10.1186/1756-8722-4-13 · 4.81 Impact Factor
  • Source
    • "FLT3-ITD mutations have been reported in 20e30% of younger adult patients with AML, and FLT3/ TKD (D835) mutations in 7% [22]. These mutations have an adverse impact on prognosis and have been reported in 71e88 % of patients with the t(6;9) [1] [9]. FLT3 mutations were present in 54% of our patients, all of whom had FLT3 eITD. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Among patients with acute myeloid leukemia (AML), the t(6;9) (p22;q34) is a rare but defined subset with a poor prognosis. We report 16 patients with the t(6;9), of whom 13 had AML, 2 had myelodysplastic syndrome (MDS), and 1 had chronic myeloid leukemia in myeloid blast crisis (CML-BC). All except for one were evaluated at diagnosis. The median age was 34.5 (range: 7-62 years), with 12 adults and 12 males. Trilineage dysplasia was present in 13 (81%). Marrow basophilia was seen in only two patients, one of whom had CML-BC. HLA-DR was positive in all 12 patients assessed, CD33 in 11, CD13 in 10, and CD34 in seven. Four patients had one other abnormality apart from the t(6;9). These were the t(9;22) in the patient with CML and deletion 9q, addition 13q, and an isochromosome 8q in the other three patients. There were no complex karyotypes. Fms-related tyrosine kinase 3--internal tandem duplication (FLT3-ITD) mutations were seen in seven of 13 patients. Follow-up details were available for six patients. Three received palliative care, and follow-up details were not available for the other seven. The response to chemotherapy was poor in the remaining patients. The only patients who survived were three out of the four who had allogeneic hematopoietic stem cell transplantation (HSCT).
    Cancer genetics and cytogenetics 12/2010; 203(2):297-302. DOI:10.1016/j.cancergencyto.2010.08.012 · 1.93 Impact Factor
Show more