Mature B-cell acute lymphoblastic leukemia with t(9;11) translocation: a distinct subset of B-cell acute lymphoblastic leukemia

Abstract

Mature B-cell acute lymphoblastic leukemia (ALL) is typically associated with the FAB-L3 morphology and rearrangement of the MYC gene, features characteristic of the leukemic phase of Burkitt's lymphoma. However, the term 'mature' has also been used to describe other rare cases of B-ALL with light-chain surface immunoglobulin expression. In contrast, infantile B-cell ALL is generally characterized by rearrangement of the MLL gene, an immature pro-B-cell phenotype, and CD10 negativity. We describe two unusual cases of infantile B-ALL with non-L3 morphology, expressing a mature B-cell phenotype (k sIg þ , CD19 þ , CD10À, TdTÀ, and CD34À), and showing MLL rearrangement without MYC rearrangement at presentation. Both infants relapsed after months of morphologic and genetic remission. At relapse, the t(9;11) translocation was detected in both cases by spectral karyotyping. After the initial relapse, both cases followed a rapid and aggressive course. Literature search identified few similar cases, all expressed k surface immunoglobulin and showed MLL rearrangement (majority with the t(9;11) translocation). These cases show that B-ALL with MLL rearrangement, especially the t(9;11) translocation, can express a 'mature' B-cell phenotype and may represent a distinct subset. Identification of additional cases will further clarify the significance of MLL rearrangements in mature B-ALL.

Mixed Lineage Leukemia–Rearranged Childhood Pro-B and CD10-Negative Pre-B Acute Lymphoblastic Leukemia Constitute a Distinct Clinical Entity

“…The only exception that we encountered was an infant suffering from a mature B-AL with FAB L1 morphology and a MLL/AF9 aberration (38). Whether the heterogeneous CD10 expression in this instance reflects an irregular differentiation of the MLL-rearranged cell population or whether only the CD10À blast cells carried the MLL rearrangement was not yet further investigated.…”

Mature B-cell lymphoblastic leukemia with MLL rearrangement: an uncommon and distinct subset of childhood acute leukemia

“…1 A subgroup of Ph þ -CML mimics ET or PMF by presenting with marked thrombocytosis or myelofibrosis (MF), but only single cases with concomitant Ph þ -CML and Ph À -CMPD were reported so far. [2][3][4][5] Recently, our group Inami et al, Krämer et al, and Bornhäuser et al [2][3][4][5] simultaneously reported on four well-documented cases with concurrent JAK2 V617F and BCR-ABL translocation ( Table 1). The tyrosine kinase abnormalities appeared to affect independent subclones because imatinib mesylate (IM) treatment induced Ph þ -CML remission whereas the JAK2 V617F clone either persisted or became clinically manifest as PMF [2][3][4] or PV.…”

“…3 Among the cases of mature B-ALL without FAB-L3 morphology and MYC rearrangement reported in children, very few present MLL gene rearrangements and especially the t(9;11) translocation. 2,4,5 We here describe an additional series of five cases of such childhood mature B-ALL with MLL rearrangement, four with the t(9;11) translocation and one with the t(10;11) translocation, and focus on their common clinical and biological characteristics.…”

“…However, rare cases of sIg þ B-ALL with non-FAB-L3 morphology and lacking MYC rearrangement have been reported in both adult and pediatric patients as 'mature B-ALL'. 1,2 Clonal rearrangements of MLL (mixed lineage leukemia or myeloid/lymphoid leukemia) gene are usually seen in infants' leukemias as well as a majority of therapy-related leukemias, in which it always represents a hallmark for aggressive disease, poor clinical outcome and bad response to treatment with high risk of relapse. 2,3 Those rearrangements include chromosomal translocations, internal gene duplications, chromosome 11q deletions or inversions, MLL gene insertions into other chromosomes and insertion of genetic material into the MLL gene.…”

“…5 In our previously reported case, a minor JAK2 V617F clone expanded after major response of Ph þ -CML to IM. 2 In search for parallel cases, we discovered a total of four CMPD cases of concurrent BCR-ABL and JAK2 V617F mutation in the Hannover bone marrow registry (Table 1). In one of these Ph þ -CML cases similar to the previously published cases, 2-5 the concurrent JAK2 V617F clone became clinically manifest subsequently to IM-induced suppression of the BCR-ABL clone.…”