CML transformation to lymphoid blast phase (BP) is associated with copy number abnormalities, characteristic of BCR-ABL1 positive acute lymphoblastic leukemia, but not of CML in the chronic phase.
The studies were conducted by using (i) primary CML-CP stem/early progenitor cells and normal hematopoietic counterparts isolated from the bone marrow of newly diagnosed patients with CML-CP and from healthy donors, respectively, (ii) CML-blast phase cell lines (K562 and KCL-22), and (iii) from <i>BCR-ABL1</i>-transformed 32Dcl3 cell line.
While most blast crises are of myeloid origin, myeloid BC with ALL-like morphologic features and Ph-positive acute myeloid leukemia (AML) is rare, especially at the time of CML diagnosis.
Bosutinib, a BCR-ABL1 tyrosine kinase inhibitor (TKI), has been available for several years as a treatment for chronic-, accelerated-, and blast-phase chronic myeloid leukemia (CML), for patients with resistance or intolerance to prior therapy.
This case illustrates the major interest of interphase FISH for BCR-ABL1 rearrangement on blood neutrophils as a decisive method to discriminate a lymphoid blast crisis of CML from a de novo BCR-ABL1 positive ALL.
Myeloproliferative neoplasms with t(8;22)(p11.2;q11.2)/BCR-FGFR1: a meta-analysis of 20 cases shows cytogenetic progression with B-lymphoid blast phase.
We report here the first use of whole-genome sequencing (WGS) to examine the initial clonal dynamics in an unusual patient with chronic myeloid leukemia (CML), who presented in chronic phase (CP) with doubly marked BCR-ABL1<sup>+</sup>/JAK2<sup>V617F</sup>-mutant cells and, over a 9-year period, progressed into an accelerated phase (AP) and then terminal blast phase (BP).
These patients have <i>BCR-ABL1</i>-positive clonal hematopoiesis resembling a chronic myeloid leukemia (CML)-like disease manifesting in "lymphoid blast crisis."
Furthermore, Gadd45a expression in samples obtained from CML patients was upregulated in more indolent chronic phase CML samples and down regulated in aggressive accelerated phase CML and blast crisisCML.
According to the 2008 World Health Organization (WHO) Classification of Tumors of the Haematopoietic and Lymphoid Tissues, the finding of B lymphoblasts in the blood or bone marrow of a patient with chronic myelogenous leukemia, BCR-ABL1+ (CML) should raise a concern for progression of the disease to B-lymphoblastic blast phase.
Here, we show that the expression of WASP decreases with the progression of CML, inversely correlates with the expression of BCR-ABL1 and is particularly low in blast crisis.
We demonstrated that expression of the Ik6 transcript, which lacked exons 3-6, was observed exclusively in BCR-ABL1(+) B ALL and lymphoid blast crisis CML (BC-CML) patients harbouring the IKZF1 Δ3-6 deletion.
Allogeneic transplantation, which over a decade ago was considered the definitive therapy for CML, is now appropriately used in cases where all TKIs are not tolerated, in cases of resistance to TKI therapy, or when the disease progresses from chronic phase to accelerated or blast phase.
In this study, we investigated the distribution and clonality of the TCR Vβ repertoire in 4 cases with imatinib-resistant CML in blast crisis (BC-CML) with abelson murine leukemia viral oncogene homolog 1 (ABL1) kinase domain mutations (KDMs).
The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC.
These LSCs or their progeny may at some stage acquire additional genetic changes that cause the leukemia to transform further, from CML-CP to a more advanced phase, which has been subclassified as either accelerated phase (CML-AP) or blastic phase (CML-BP).
Patients with chronic myelogenous leukemia (CML) in blast crisis have a poor response to tyrosine kinase inhibitors designed to inhibit the breakpoint cluster region-v-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) oncogene.
Distinct groups were examined: (1) acquired clinical resistance because of blast crisis and/or BCR-ABL1 mutations; and (2) documented imatinib discontinuation/interruption.
In rare cases of myeloid malignancies, the BCR-ABL1 fusion was reported to cooperate as class-I-mutation with class-II-mutations, but most cases had to be classified as blast phase of chronic myeloid leukaemia (CML).