Late appearance of the Philadelphia chromosome with monosomy 7 in a patient with de novo AML with trilineage myelodysplasia

Abstract

We report here a patient with de novo acute myelocytic leukemia with trilineage myelodysplasia (AML/TMDS) in whom cytogenetic analysis was normal at diagnosis and in whom Philadelphia chromosome (Ph1) with monosomy 7 emerged at the terminal stage of the disease. Reverse transcription polymerse chain reaction (RT-PCTR) on the Ph1 positive specimen detected the mRNA encoding p190bcr/abl but did not detect mRNA encoding p210bcr/abl. However, mRNA encoding p190bcr/abl was not detected at diagnosis and or at relapse. These observations support the hypothesis that late-appearing Ph1 and monosomy 7 might be the result of clonal evolution during the course of leukemia, and p190bcr/abl might play a role in the terminal transformation or progression of leukemia.

Clonal development of myeloproliferative disorders: clues to hematopoietic differentiation and multistep pathogenesis of cancer

“…These cells thereby gain great selective advantage and specific leukemic properties. The observation that Ph 1 occasionally arises late in the course of Phnegative CML, [45][46][47] myelodysplastic syndromes [48][49][50][51] or acute leukemia supports this hypothesis. [52][53][54][55] In contrast, it is possible that some cases of Ph-negative or mixed blast crisis following Ph-positive CML 56,57 occur when a coexisting subclone gains dominance over the Ph-positive chronic phase cells.…”

Expression ofBCR/ABLandBCL-2in myeloid progenitors leads to myeloid leukemias

“…For each reaction, RNA was extracted from a starting population of 1,000 cells by using MS2 phage carrier RNA (Roche Molecular Biochemicals) as reported (25). Reverse transcription and subsequent semiquantitative, nested PCR for p210 BCR/ABL (26) and murine Mrp8 (27) were performed as described.…”

Acquisition of the Ph chromosome and BCR-ABL fusion product in AML-M2 and t(8;21) leukemia: cytogenetic and FISH evidence for a late event

“…[6][7][8][9] Although the late appearance of the Ph chromosome in AML is unusual there are several documented cases in the literature, including two patients that we previously reported in whom the Ph first emerged during the first and second relapse, respectively. 4,5,10 To our knowledge the patient described in this report is the first patient with AML in whom the late appearance of the Ph and BCR-ABL fusion appeared in a clone characterized by t(8;21). The results of a literature survey of the molecular analysis of late appearing Ph chromosome in eight patients with AML are shown in Table 2.…”

“…In five reported patients with AML and a late appearing Ph chromosome, RT-PCR assay did not detect a BCR-ABL fusion transcript at the time of diagnosis, but only concurrent with the cytogenetic appearance of the late appearing Ph chromosome. 4,[11][12][13][14] A recent publication has suggested a possible causal relationship between chemotherapy with DNA topoisomerase II inhibitors and the subsequent development of leukemia with t(9;22). 15 In these 25 reported patients the latent period was between 4 and 192 months.…”

“…1,2 In acute myelogenous leukemia (AML), the late appearance of the Ph is an even more unusual event. [3][4][5] We recently studied a patient with the M2 subtype of AML and a 45,X,−X,t(8;21) karyotype at diagnosis who developed the Ph chromosome 18 months later. The BCR-ABL fusion product was not detected by interphase FISH analysis 4 months prior to the cytogenetically evident Ph chromosome.…”