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ALL-1 Gene Rearrangements in Acute Myeloid Leukemia: Association with M4–M5 French-American-British Classification Subtypes and Young Age¹

Dipartimento di Biopatologia Umana, Sezione di Ematologia, University "La Sapienza," Via Benevento 6, 00161 Rome, Italy [G. C., M. C. R., L. E., A. M. T., S. T., F. M.]; Clinica Pediatrica, Ospedale S. Gerardo, University of Milan, Milan, Italy [A. B.]; Clinica Medica, Policlinico Monteluce, University of Perugia, 06100 Perugia, Italy [M. F.]; Jefferson Cancer Institute, Jefferson Cancer Center, and Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 [C. M. C.]; and Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel [E. C.]

We have analyzed by Southern blotting the ALL-1 (MLL, HRX, Hrtx 1) gene configuration in a series of 126 patients with acute myeloid leukemia (AML) representative of all ages and French-American-British Classification groups and correlated this genetic feature with clinical and biological features at diagnosis. ALL-1 gene rearrangements were detected in 17 of the 74 cases with M4–M5 (myelomonocytic and monocytic) AML and in 2 of the 52 cases with other leukemic subtypes (P < 0.01). Within the series of 74 M4–M5 patients, ALL-1 rearrangements were significantly associated with French-American-British Classification M5 (P = 0.009), high WBC (P = 0.002), and young age. In particular, all 5 infant (<1.5 years) AML cases, 6 of the 19 (31%) patients between 1.5 and 18 years of age, and 6 of the 50 (12%) patients >18 years old showed an altered ALL-1 genomic configuration (P < 0.001). Immunophenotypic characterization revealed coexpression of lymphoid and myeloid markers in 6 of 17 ALL-1 rearranged M4–M5 cases.

The IgH gene configuration was studied in 77 of 126 AMLs. Five patients (6%) showed IgH clonal rearrangements and all were in the ALL-1 rearranged group (P < 0.0001).

Our findings indicate that ALL-1 rearrangement is the commonest genetic alteration presently detectable in M4–M5 AML, particularly in childhood where it is found in up to one-third of all cases. The association of IgH rearrangements with ALL-1 alterations in AML, coupled to the frequent detection in this subset of lymphoid associated markers, further supports the origin of these tumors from a common multipotent precursor with bipotential lymphoid and monocytic differentiation capability.

¹ Supported in part by the Associazione Italiana Ricerca Cancro (AIRC) and by Consiglio Nazionale delle Ricerche (PF ACRO).

² To whom requests for reprints should be addressed, at Department of Human Biopathology, University "La Sapienza," Via Benevento 6, 00161 Rome, Italy.

Received 2/15/95. Accepted 3/ 6/95.

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