AML (Acute Myelogenous Leukemia): Is it still a major group of childhood cancer with the worst overall survival rate?

1. Does it depend on patient’s CR (Complete Remission)?

2. Whether an elevated CR rates not necessarily get translated into an enhanced survival?

3. If so, then, upon discovering relapse, the application of standard regimens, or, investigational therapy – necessarily depends on initial remission of the patient?

4. What is the primary cause behind childhood malignancy occurring within any blood cell lineage? Even in childhood, why does hematologic malignancy become a genetically heterogeneous disease, despite being characterized by bone marrow infiltration with abnormally differentiated and proliferating cells of hematopoietic origin? In such cases, why do we include allogenic HSCT (even, for patients, with adverse molecular or cytogenetic aberrations)?

5. Why does the occurrence of AML in children remain to be biphasic? What exactly is happening between 4th year and 13thyear (in a relative sense) that circumvents the occurrence of AML?

If so, then, how could cancer develop in a hierarchical manner from cancer stem cells that self-renew and give rise to a differentiated cell progeny by asymmetric division?

If not, then, AML development no more recapitulates the normal hematopoietic hierarchy?

6. Why do we have the dominance of ALL (Acute Lymphoblastic Luekemia) particularly between 2 and 5 years of age; while, AML has a consistent occurrence throughout the childhood?

7. Is there a specific trend or relation between ALL, AML & Lymphoma as a function of age that covers both childhood and adolescence? Would this relation become further complex clinically and histologically, if marrow and lymph involvement are present simultaneously during diagnosis?

8. What will be status and behavior of T-Lymphocytes on the onset of a genomic alteration within a particular blood cell lineage (either in immature progenitor stage or during a mature stage of cellular differentiation)?

9. Whether the interaction between CXCR4 on leukemia progenitors and CXCL12 on bone marrow stromal cell ‘always favor’ Leukemia Stem cells homing to bone marrow micro-environment?

10. What are the favorable circumstances under which leukemic cells tend to remodel the bone marrow stromal cells in order to generate a shelter for disease progression?

11. If AML-EVs could modulate both cellular and molecular properties of normal MSCs, then, is there no way to circumvent this disease relapse? Is there a way to arrest the modifications of bone marrow micro-environment, while allowing the alterations of normal hematopoietic cells only?

Suresh Kumar Govindarajan

Professor (HAG)

IIT Madras

https://home.iitm.ac.in/gskumar/

https://iitm.irins.org/profile/61643

24-Aug-2024