Philadelphia-Chromosome-Positive T-Lymphoblastic Leukemia: Acute Leukemia or Chronic Myelogenous Leukemia Blastic Crisis

Abstract

The Ph1 chromosome has rarely been reported in T-lineage acute lymphoblastic leukemia (T-ALL), and the clinical relevance of this translocation in T-ALL is currently unknown. In chronic myelogenous leukemia (CML) some data indicate derivation of T-cells from the leukemic clone and only a few cases of T-derived blastic crisis have been reported and quite often disputed. Particularly in cases identified initially in blastic crisis it may be difficult to distinguish those from Ph1-positive T-ALL. We herein report 2 patients who presented with a clinical picture of Ph1-positive T-ALL and who raised a differential diagnosis from T-cell blastic crisis of CML. We review the literature and suggest clinical and laboratory features that can help in the diagnosis. According to our literature review, 23 cases of Ph1-positive T-ALL and 44 cases of T-cell blastic crisis of CML, including ours, were reported. Some major differences between the two entities could help in establishing a diagnosis of Ph1-positive T-cell blastic crisis of CML vs. Ph1-positive T-ALL: Male sex and younger age was more predominant in T-ALL. While in most cases of CML blastic crisis there was a history of CML there was no such history in the T-ALL cases. Medullary involvement with lymphoblastic leukemia was present in all cases of T-ALL but only in about half of the cases of CML blastic crisis. None of the CML-blastic crisis cases tested by RT-PCR showed the minor breakpoint transcript, while 2 cases with T-ALL had the minor breakpoint transcript and 1 had both transcripts. Combined morphologic and FISH analysis can help to distinguish between the two entities and was applied in one of our cases. Although both entities carry a severe prognosis, differentiating between them might have clinical relevance, especially in the imatinib era.

The spectrum of adult B‐lymphoid leukemias with BCR‐ABL: Molecular diagnostic, cytogenetic, and clinical laboratory perspectives

“…Specifically, adult patients with Ph-chromosomepositive acute leukemia with expression of the p210 isoform of BCR-ABL may have a de novo p210-ALL or CML in lymphoblastic crisis that had an indolent chronic phase. Although other published studies have evaluated the differences between blast phase CML and de novo Ph-positive acute myeloid leukemias [12] and de novo Ph-chromosome-positive T-lymphoblastic leukemias [13], to our knowledge, no comprehensive study exists for distinguishing lymphoblastic CML from Ph1 adult B-ALL. The limited nature of histopathologic studies of lymphoid blast phase CML is likely due to the relative rarity of this form of Ph-chromosome-positive leukemia.…”

MOHITO, a novel mouse cytokine-dependent T-cell line, enables studies of oncogenic signaling in the T-cell context

“…In order to test if the IL-7 dependent MOHI-TO cell line would serve as a model system to study kinase signaling in the T-cell context, we tested if MOHITO cells could be transformed to IL-7 independent proliferation by BCR-ABL1 or the JAK1(A634D) mutant, two oncogenes known to be implicated in the pathogenesis of T-ALL. 3,[22][23][24] We transduced MOHITO cells with a bicistronic BCR-ABL1-IRES-GFP construct allowing us to track BCR-ABL1 expressing cells by GFP. With an initial fraction of about 30% GFP positive cells, cytokine withdrawal caused a constant increase of the GFP positive population, which finally completely outcompeted the untransduced cells ( Figure 3A).…”

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia<b> </b>Is Separated into Two Subgroups Associated with Survival by <b><i>BCR</i></b>-<b><i>ABL</i></b> Fluorescence in situ Hybridization of Segmented Cell Nuclei: Report from a Single Institution

“…In principle, Ph+ ALL is restricted to the lymphoid lineage without affecting other lineage cells. In contrast, since CML is a hematopoietic stem cell disorder, it is assumed that not only lymphoblasts, but also myeloid lineage cells have the ability to carry the BCR - ABL fusion gene in lymphoid CML-BC [15,16,17]. In the present study, we applied fluorescence in situ hybridization (FISH) of the BCR - ABL fusion gene to PB and/or BM smear slides at presentation.…”