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MLL and CALM Are Fused to AF10 in
Morphologically Distinct Subsets of Acute Leukemia With
Translocation t(10;11): Both Rearrangements Are Associated With a
Poor Prognosis
M.H. Dreyling,
K. Schrader,
C. Fonatsch,
B. Schlegelberger,
D. Haase,
C. Schoch,
W.-D. Ludwig,
H. Löffler,
T. Büchner,
B. Wörmann,
W. Hiddemann, and
S.K. Bohlander
From the Department of Hematology/Oncology, University of
Göttingen, Göttingen, Germany; the Institute of Medical
Biology, University of Vienna, Vienna, Austria; the Institute of Human
Genetics, University of Kiel, Kiel, Germany; the
Robert-Rössle-Clinic, Department of Hematology/Oncology and Tumor
Immunology, Humboldt-University of Berlin, Berlin, Germany; the
Department of Medicine, University Hospital of Kiel, Kiel,
Germany; the Department of Hematology/Oncology, University of
Münster, Münster, Germany; and the Institute of Human
Genetics, University of Göttingen, Göttingen, Germany.
The translocation t(10;11)(p13;q14) has been observed in acute
lymphoblastic leukemia (ALL) as well as acute myeloid leukemia (AML). A
recent study showed a MLL/AF10 fusion in all cases of AML with
t(10;11) and various breakpoints on chromosome 11 ranging from q13 to
q23. We recently cloned CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene), the fusion partner of AF10 at 11q14 in the monocytic cell line U937. To further define the role of these genes
in acute leukemias, 10 cases (9 AML and 1 ALL) with cytogenetically proven t(10;11)(p12-14;q13-21) and well-characterized morphology, immunophenotype, and clinical course were analyzed. Interphase fluorescence in situ hybridization (FISH) was performed with 2 YACs
flanking the CALM region, a YAC contig of the MLL
region, and a YAC spanning the AF10 breakpoint. Rearrangement
of at least one of these genes was detected in all cases with balanced
t(10;11). In 4 cases, including 3 AML with immature morphology (1 AML-M0 and 2 AML-M1) and 1 ALL, the signals of the CALM YACS
were separated in interphase cells, indicating a translocation
breakpoint within the CALM region. MLL was rearranged
in 3 AML with myelomonocytic differentiation (2 AML-M2 and 1 AML-M5),
including 1 secondary AML. In all 3 cases, a characteristic
immunophenotype was identified (CD4+,
CD13 , CD33+, CD65s+).
AF-10 was involved in 5 of 6 evaluable cases, including 1 case without detectable CALM or MLL rearrangement. In 2 complex translocations, none of the three genes was rearranged. All
cases had a remarkably poor prognosis, with a mean survival of 9.6 ± 6.6 months. For the 7 AML cases that were uniformly treated according
to the AMLCG86/92 protocols, disease-free and overall survival was
significantly worse than for the overall study group (P = .03 and P = .01, respectively). We conclude that the
t(10;11)(p13;q14) indicates CALM and MLL rearrangements
in morphologically distinct subsets of acute leukemia and may be
associated with a poor prognosis.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4662-4667
© 1998 by The American Society of Hematology.
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