A de novo acute myeloid leukemia (AML-M4) case with a complex karyotype and yet unreported breakpoints

Abstract

Background: Acute myelogeneous leukemia (AML) is a malignancy of the hematopoietic stem cells, for which cytogenetic analysis is still one of the most important diagnostic and prognostic tools. Still, we are far away from having seen and described all possible genetic changes associated with this kind of acquired disease.

Results: Bone marrow cells of a female patient with clinical diagnoses of AML and immunophenotypically confirmed AML-M4 were studied by GTG-banding. The later was not able to resolve all karyotypic changes and the complex karyotype was characterized in more detail by fluorescence in situ hybridization (FISH) and array-proven multicolor banding (aMCB). To the best of our knowledge, the present case is the only one ever seen with a del(5)(q14q34), a der(17)t(4;17)(p13;p13), a del(2)(p23), a der(4)t(4;7)(p13;q11.23), a der(22)t(11;22)(q23;q11.2) and two complex rearranged chromosomes 11 involving chromosomes 7 and 22 as well as 2.

Conclusions: The yet unreported breakpoints observed in this case seem to be correlated with an adverse prognosis. Overall, molecular cytogenetic studies are suited best for identification and characterization of chromosomal rearrangements in acute leukemia and single case reports as well as large scale studies are necessary to provide further insides in karyotypic changes taking place in human malignancies.

Figure 1

GTG-banding revealed a complex karyotype involving six chromosomes and monosomy 7. All derivative or clonally missing chromosomes are highlighted by arrowheads.

Figure 2

FISH-results using locus-specific probes. (A) Metaphase FISH using probes for BCR (green) and ABL (orange) showed two orange signals on the two chromosomes 9, one green on the chromosome 22 and the other green signal was observed on der(11). (B) Metaphase FISH using probes for BCR (yellow) and ABL (red) mixed with MLL break-apart probe showed one fusion signal was located on the short arm of der(11), the second fusion signal was observed on der(22), two orange signals on the two chromosomes 9, one green on the chromosome 22 and the other green signal was observed on der(11). Abbreviations: # = chromosome; der = derivative chromosome.

Figure 3

Array-proven multicolor banding (aMCB) was applied to determine the involved in this complex rearrangement. In each lane the results of aMCB analysis using probe-sets for chromosomes 2, 4, 5, 7, 11, 17 and 22 are shown. The normal chromosomes are shown in the first column, the derivative of all five chromosomes in the following ones. In the light gray by aMCB-probes unstained regions on the derivative chromosomes are depicted. Abbreviations: # = chromosome; der = derivative chromosome.