&lt;b&gt;&lt;i&gt;BCR/ABL1&lt;/i&gt;&lt;/b&gt;-Like Acute Lymphoblastic Leukemia: From Diagnostic Approaches to Molecularly Targeted Therapy

Płotka, Anna; Lewandowski, Krzysztof

doi:10.1159/000519782

Cited by 8 publications

(7 citation statements)

References 71 publications

(142 reference statements)

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“…The increased frequency of MRD positivity in the BCR::ABL1 ‐like ALL cases reflects the aggressive clinical behavior of this subtype. This concurs with recently published works citing high rates of induction failure or MRD positivity in BCR::ABL1 ‐like B‐ALLs 6,53,99 . Novel therapies and personalized treatment regimens need to be incorporated to improve the treatment outcomes of newly incorporated entities.…”

Section: Discussionsupporting

confidence: 87%

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Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B‐lineage acute lymphoblastic leukemia: A report of 1021 patients from India

Gupta

Varma

Sharma

et al. 2023

Cancer

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BackgroundThe published literature on hematological, clinical, flowcytometric‐immunophenotyping, and minimal residual disease outcomes of the prognostically important genetic subtypes of acute lymphoblastic leukemia (ALL) is scarce from low‐income countries. For newer classifications such as BCR::ABL1‐like ALLs, the scarcity of patient‐level data is even more pronounced.MethodsThe authors performed comprehensive detection of recurrent gene fusions and BCR::ABL1‐like ALL cases followed by immunophenotypic profiling and obtained clinical outcome parameters for a large cohort (n = 1021) of patients from India. This cohort included a significant number of patients with BCR::ABL1‐like ALL subtype and other genetic subtypes of ALL.ResultsPatients with BCR::ABL1‐positive and BCR::ABL1‐like ALL were significantly older, had male preponderance, and expressed a higher white blood cell count than BCR::ABL1‐negative cases (p < .05). Logistic regression modeling of B‐lineage‐ALL (B‐ALL) subtypes revealed that cluster of differentiation (CD)36 is a strong statistically significant predictive marker of BCR::ABL1‐like ALL (p < .05). Furthermore, patients with BCR::ABL1‐like ALLs show a significantly higher frequency of CD36 expression compared to BCR::ABL1‐negative ALLs (p < .05). In terms of clinical symptoms, lymphadenopathy is a strong statistically significant predictive marker in BCR::ABL1‐like ALLs compared to BCR::ABL1‐negative ALL cases (p < .05). In terms of treatment outcomes, minimal residual disease (MRD) positivity in BCR::ABL1‐positive ALL cases were statistically significant (p < .05), and BCR::ABL1‐like ALL cases had high MRD‐positivity as compared to BCR::ABL1‐negative ALL cases but did not show statistical significance.ConclusionsThe findings evince the use of novel therapies and personalized treatment regimens to improve the overall survival of the newer incorporated entities in B‐ALLs. This is the first report characterizing the hematological, clinical, flowcytometric‐immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes of ALLs in patients from India.Plain Language Summary Characterizing the hematological, clinical, flowcytometric‐immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes (n = 1021) of acute lymphoblastic leukemia (ALLs) in patients from India. We have made two independent logistic regression models of cluster of differentiation (CD) markers and clinical symptoms to differentiate prognostically significant subtypes of ALLs. Logistic regression analysis of CD markers revealed CD36 as a strong predictor in BCR::ABL1‐like ALL cases compared to BCR::ABL1‐negative ALL cases. Logistic regression analysis of clinical symptoms revealed lymphadenopathy significantly predicts BCR::ABL1‐like ALLs (p < .05). In terms of treatment outcomes, BCR::ABL1‐positive ALL had statistically significant minimal residual disease (MRD) (p < .05), and BCR::ABL1‐like ALL cases had high MRD‐positivity but did not show statistical significance as compared to BCR::ABL1‐negative ALLs.

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Section: Discussionsupporting

confidence: 87%

“…This concurs with recently published works citing high rates of induction failure or MRD positivity in BCR::ABL1-like B-ALLs. 6,53,99 Novel therapies and personalized treatment regimens need to be incorporated to improve the treatment outcomes of newly incorporated entities.…”

Section: Discussionmentioning

confidence: 99%

Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B‐lineage acute lymphoblastic leukemia: A report of 1021 patients from India

Gupta

Varma

Sharma

et al. 2023

Cancer

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“…As such, because Ph-like patients are associated with a high risk of relapse, Allo-HSCT might be of value as a consolidation modality for these patients, especially in patients who expected to have a low risk of transplant-related complications. However, there is insufficient data on the outcomes of Allo-HSCT for Ph-like ALL, and it remains debatable whether all adult Ph-like ALL patients should receive an allogeneic HSCT in the first CR, irrespective of other indications So far, no recommendations on the use Allo- HSCT have been established in Ph-like ALL patients in the CR1 [ 44 , 81 ].…”

Section: Role Of Hematopoietic Stem Cell Transplantation Based On Mrd...mentioning

confidence: 99%

Philadelphia-like acute lymphoblastic leukemia: the journey from molecular background to the role of bone marrow transplant—review article

2023

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Philadelphia chromosome-like (Ph-like) ALL is a recent subtype of acute lymphoblastic leukemia. Although it does not express the BCR-ABL fusion gene, it has a behavior like true BCR/ABL1–positive cases. This subtype harbors different molecular alterations most commonly CRLF2 rearrangements. Most cases of Ph-like ALL are associated with high white blood cell count, high minimal residual disease level after induction therapy, and high relapse rate. Efforts should be encouraged for early recognition of Ph-like ALL to enhance therapeutic strategies. Recently, many trials are investigating the possibility of adding the tyrosine kinase inhibitor (TKI) to chemotherapy to improve clinical outcomes. The role and best timing of allogeneic bone marrow transplant in those cases are still unclear. Precision medicine should be implemented in the treatment of such cases. Here in this review, we summarize the available data on Ph-like ALL

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“…A wide spectrum of genetic alterations has been described in Ph-like B-ALL cases including translocations, cryptic gene rearrangements, sequence mutations and copy number changes. The majority of these alterations lead to constitutively active kinase or cytokine receptor signaling, and many of them have been shown to be druggable with a variety of TKIs (Table 2) (31,32). Founder mutations may be classified into four groups:…”

Section: Bcr::abl1 Fusion-like (Ph-like)mentioning

confidence: 99%

Prognostic and Predictive Biomarkers in Precursor B-cell Acute Lymphoblastic Leukemia

Zhang

Habeebu

2022

Leukemia

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Precursor B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic malignancy characterized by clonal proliferation of abnormal B-cell precursors in the bone marrow. Most of the B-ALL cases are diagnosed in children, although it can present at any age. Thanks to the tremendous advances in our understanding of its biology, identification of more and more prognostic and predictive biomarkers, and application of individualized risk-adjusted treatment, B-ALL has become the most curable malignancy in children, with a long-term survival rate close to 90% in newly diagnosed Note to the Reader: This chapter is part of the book Leukemia (ISBN: 978-0-6453320-7-0), scheduled for publication in September 2022. The book is being published by Exon Publications,

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<b><i>BCR/ABL1</i></b>-Like Acute Lymphoblastic Leukemia: From Diagnostic Approaches to Molecularly Targeted Therapy

Cited by 8 publications

References 71 publications

Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B‐lineage acute lymphoblastic leukemia: A report of 1021 patients from India

Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B‐lineage acute lymphoblastic leukemia: A report of 1021 patients from India

Philadelphia-like acute lymphoblastic leukemia: the journey from molecular background to the role of bone marrow transplant—review article

Prognostic and Predictive Biomarkers in Precursor B-cell Acute Lymphoblastic Leukemia

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