MYC rearranged B-cell neoplasms: Impact of genetics on classification.
A cohort comprising 156 patients with B-cell neoplasms harboring an MYC rearrangement was analyzed with respect to phenotypic presentation, molecular markers (TP53, MYC and ID3) and additional cytogenetic abnormalities (concomitantly occurring BCL2, BCL6 and/or CCND1 rearrangements; double, triple or quadruple hit lymphomas = multiple hit lymphomas). MYC translocations occurred as single hit (only MYC rearranged, 63%) or multiple hit lymphoma (37%) and presented as acute leukemia (AL) (14%), Burkitt lymphoma (30%), chronic lymphocytic leukemia (CLL) (21%) or other mature B-cell neoplasms (35%). Multiple hit lymphomas more frequently showed a complex karyotype compared to single hit lymphomas (62% vs. 28%, p < 0.001). Single hit Burkitt lymphomas presented with specific characteristics, by translocation of MYC to an immunoglobulin locus, predominantly a non-complex karyotype (23% vs. 67%, p = 0.012) and a significantly higher ID3 and TP53 mutation frequency (ID3mut: 49% vs. 0%, p = 0.002; TP53mut: 69% vs. 33%, p = 0.045). Additionally, MYC rearranged CLL presented as outstanding group by often showing a non-complex karyotype (85%), absence of ID3 mutations, a high frequency of SF3B1 mutations, and a frequent involvement of non-immunoglobulin loci as MYC-partner genes (61%). Consequently, genetic characteristics distinguish different subgroups of MYC rearranged B-cell neoplasms and therefore may contribute to a new classification system.
MLL Munich Leukemia Laboratory, Munich, Germany.
Sabine
S
Haberl
MLL Munich Leukemia Laboratory, Munich, Germany.
Torsten
T
Haferlach
MLL Munich Leukemia Laboratory, Munich, Germany.
Anna
A
Stengel
MLL Munich Leukemia Laboratory, Munich, Germany.
Sabine
S
Jeromin
MLL Munich Leukemia Laboratory, Munich, Germany.
Wolfgang
W
Kern
MLL Munich Leukemia Laboratory, Munich, Germany. Electronic address: claudia.haferlach@mll.com.
Claudia
C
Haferlach
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D002869:Chromosome Aberrations; D015331:Cohort Studies; D019938:Cyclin D1 / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult
C000595707:BCL2 protein, human; C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1
B-cell neoplasms; Burkitt lymphoma; CLL; Double hit lymphoma; MYC rearrangement