CongenitalMLL-positive B-cell acute lymphoblastic leukemia (B-ALL) switched lineage at relapse to acute myelocytic leukemia (AML) with persistent t(4;11) and t(1;6) translocations and JH gene rearrangement

Abstract

Congenital acute leukemia is a rare form of childhood leukemia, in which lineage conversion at relapse is very rarely reported.Here we describe a case of congenital B-cell acute lymphoblastic leukemia (B-ALL) with t(4;11) and t(1;6) translocations, which at relapse underwent a switch to monocytic lineage with persistence of the original cytogenetic translocations and clonal rearrangement of the JH gene. Similar to the other described cases of congenital acute leukemia with lineage conversion, our case had a MLL gene rearrangement and followed an aggressive clinical course.

Lineage switch in childhood acute leukemia: An unusual event with poor outcome

“…The mostly single case pediatric reports in the literature also support this notion, describing switches from Bcp to myelo-monocytic lineages [5,6,9,25,26,[31][32][33][34][35][36][37]. Conversions from AML (or bilineal) to ALL are even more rare [38][39][40][41][42][43], also involve mostly Bcp and myelo-monocytic lineages, as was the case with the 2 patients from our own series that switched from myeloid to Pro-B.…”

“…A report of a lineage conversion case shows involvement of chromosome 6 together with MLL [6] but in Case 5 of our series chromosome 6 deletion was the only alteration detected. Unfortunately, it was not possible to perform other analyses as Southern Blot, MLL dual color split FISH or long distance inverse PCR to rule out the presence of MLL gene involvement in the two MLL negative patients.…”

“…Furthermore, three of them were even younger than 1 month of age, a fact that implies the in utero development of the leukemia [6,25].…”

“…One possible explanation could be the ''selection'' of a preexistent chemotherapy-insensitive minor population of cells of different lineage among the predominant population of leukemic blasts at diagnosis (biphenotypic or bilineal leukemias) with the consequent emergence of the resistant ''sub-clone'' expressing a different repertory of antigens [6]. Another possibility might be the reprogramming of a malignant pluripotent stem cell, or rather, taking into account the most frequently involved cell types in these conversions, of a common bipotent B-myeloid precursor [7,8].…”

Clinical features, molecular diagnosis, and treatment outcome of infants with leukemia in Taiwan

“…Most often, the time between initial diagnosis and lineage switch is 1-4 years [43], while the time interval in our 2 patients was shorter (12 days and 4.4 months, respectively). A lineage switch can occur sooner (less than 1 year after diagnosis) in neonates with leukemia [44,45].…”