Short communicationInsertion of chromosome 11 in chromosome 4 resulting in a 5′MLL-3′AF4 fusion gene in a case of adult acute lymphoblastic leukemia
Introduction
The t(4;11)(q21;q23) occurs in 3%–6% of adult acute lymphoblastic leukemia (ALL) and is associated with a poor prognosis [1], [2]. It results in the fusion of the MLL gene located in 11q23 to the AF4 gene on 4q21 and generates a 5′MLL-3′AF4 fusion gene on the derivative chromosome 11. The chimeric transcript of this fusion gene can be detected by reverse transcriptase polymerase chain reaction (RT-PCR) [3], [4].
A few patients with the 5′MLL-3′AF4 rearrangement lacking or associated with a variant or complex t(4;11) have now been described [5], [6], [7], [8]. We report here the insertion of material of a chromosome 11 into a chromosome 4 resulting in the location of the 5′MLL-3′AF4 fusion gene on the derivative chromosome 4.
Section snippets
Case report
A 69-year-old woman was first seen for treatment of ALL associated with a severe diffuse intravascular coagulopathy. Neither adenopathies nor hepatosplenomegaly were noted during the physical examination upon admission. Hematologic data were as follows: hemoglobin 11.4 g/dL; and white blood cell (WBC) counts 75.8×109/L with 77.5% blast cells, 12.5 lymphocytes, 5% neutrophils, 2% monocytes, and platelets 46×109/L.
The bone marrow aspirate showed hypercellularity, with 90% lymphoblasts having a
Conventional cytogenetics
Cytogenetic analysis with R-banding of the patient's bone marrow cells was performed at the time of diagnosis and at the time of complete hematologic remission, as previously described [9].
Molecular cytogenetics
Dual-color fluorescence in situ hybridization (FISH) was performed using whole chromosome painting (WCP) probes specific to chromosome 4 (WCP4 labeled with SpectrumRed; Qbiogene, Illkirch, France) and chromosome 11 (WCP11 labeled with digoxygenin; Qbiogene), as previously described [9]. Direct
Results
Cytogenetic studies with R banding showed a 46,XX,ins(4;11)(q21;q13q23)[3]/46,idem,−22,+mar[18] karyotype in the bone marrow culture (Fig. 1).
FISH analysis with wcp4 and wcp11 confirmed the insertion of part of a chromosome 11 in the long arm of a chromosome 4 (Fig. 2). Using MLL dual-color probes, the portion centromeric of the MLL gene bcr (SpectrumGreen) was found on the der(4) whereas the portion telomeric of bcr (SpectrumOrange) was on the der(11) (Fig. 3). Thus, the derivative chromosomes
Discussion
The patient reported here had several features, including high white blood cell and blast counts with a pre-B phenotype (CD19+, CD10−), which are usually observed in patients carrying the t(4;11) [8].
A review of the literature identified two cases, which were reported before the MLL-AF4 fusion gene was recognized, involving an insertion between chromosomes 4 and 11. In the first case, band q23 of a chromosome 11 was inserted in band q21 of a chromosome 4 [12] and in the second, it was part of
Acknowledgements
The authors thank Nadia Guéganic, Marie-Françoise Scoazec, Nicole Pichavant, and Pierre Roudaut for their skillful technical assistance.
References (14)
- et al.
Clinical significance of cytogenetic abnormalities in adult acute lymphoblastic leukemia
Blood
(1998) - et al.
The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophilia trithorax, to the AF-4 gene
Cell
(1992) - et al.
Detection of ALL-1/AF4 fusion transcript by reverse transcription-polymerase chain reaction for diagnosis and monitoring of acute leukemias with the t(4;11) translocation
Blood
(1993) - et al.
Clinical significance of MLL-AF4 fusion transcript expression in the absence of a cytogenetically detectable t(4;11)(q21;q23) chromosomal translocation
Blood
(1998) - et al.
AML1 amplification in a case of childhood acute lymphoblastic leukemia
Cancer Genet Cytogenet
(2002) - et al.
Leukemia with a novel 4q11q rearrangement
Cancer Genet Cytogenet
(1985) - et al.
Acute lymphoblastic leukemia with a unique rearrangement between chromosomes 4 and 11
Cancer Genet Cytogenet
(1988)
Cited by (22)
Cytogenetics in pre-B and B-cell acute lymphoblastic leukemia: a study of 208 patients diagnosed between 1981 and 2008
2010, Cancer Genetics and CytogeneticsCitation Excerpt :Cytogenetic analysis was performed on bone marrow cells at the time of diagnosis, relapse, or both. Briefly, the bone marrow unstimulated 24 hour-culture was synchronized with fluorouridine (10−7 mol/L) for 17 hours followed by thymidine (10−5 mol/L) for 6 hours before exposure to Colcemid and standard harvesting [4]. The chromosomes were R-banded, and the karyotype was described according to ISCN 1995 [5], the standard in effect through most of the period and still applicable in the final years of the study period.
Complex and cryptic chromosomal rearrangements involving the MLL gene in acute leukemia: A study of 7 patients and review of the literature
2010, Blood Cells, Molecules, and DiseasesMLL insertion with MLL-MLLT3 gene fusion in acute leukemia: case report and review of the literature
2008, Cancer Genetics and CytogeneticsCitation Excerpt :In contrast to the classic t(9;11)(p21;q23) (the principal cause of a MLL-MLLT3 fusion; Fig. 3A3), no reciprocal gene fusion could be detected in the insertion cases. MLL insertions implicated various chromosome arms, such as Xq [9–16], 1q [17,18], 2q [19], 3p [20], 4q [17,21–24], 5q [25–27], 6q [17,28,29], 9q [30], and 10p [31–42] (Table 1). The insertions involving MLL result in most of the reported cases in fusion genes, but insertions of MLL without evidence of MLL gene fusion were also reported [43–45].
Translocation (10;17)(p15;q21) is a recurrent anomaly in acute myeloblastic leukemia
2007, Cancer Genetics and Cytogenetics