ALL-1 gene rearrangements in acute myeloid leukemia: association with M4-M5 French-American-British classification subtypes and young age.
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.
Cimino
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Dipartimento di Biopatologia Umana, University La Sapienza, Rome, Italy.
Rapanotti
M C
MC
Elia
L
L
Biondi
A
A
Fizzotti
M
M
Testi
A M
AM
Tosti
S
S
Croce
C M
CM
Canaani
E
E
Mandelli
F
F
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005602:France; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D007948:Leukemia, Monocytic, Acute / Q000145:classification / Q000235:genetics* / Q000276:immunology; D015479:Leukemia, Myelomonocytic, Acute / Q000145:classification / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein; D011519:Proto-Oncogenes; D015183:Restriction Mapping; D014157:Transcription Factors; D006113:United Kingdom; D014481:United States; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase